Proliferation Of Oral Cancer Cells Research Articles

Let-7 reduces the proliferation and migration of oral cancer cells via PI3K/AKT signaling pathway.

The involvement of let-7 in the occurrence and progression of various cancers has been well-documented. However, the precise molecular mechanisms underlying its impact on oral cancer development remain unclear. In this study, we aimed to elucidate the role of let-7 in oral cancer progression and investigate its underlying molecular mechanisms. The expression of let-7 and high mobility group A2 (HMGA2) mRNA was assessed using the quantitative reverse transcription polymerase chain reaction. Western blot analysis was employed to detect the expression of key proteins in the PI3K/AKT signaling pathway as well as HMGA2 protein levels. The targeting relationship between let-7 and HMGA2 was predicted through bioinformatics methods and confirmed via luciferase reporter gene assay. The effects of let-7 and HMGA2 on the functionality of oral cancer cells were evaluated using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, colony formation assay, Transwell assay, wound healing assay, and Annexin V/PI apoptosis assay. Additionally, the impact of let-7 on the growth of oral cancer cells in vivo was investigated by inducing subcutaneous tumor formation in nude mice. Let-7 effectively suppresses the proliferation, migration, and invasion of oral cancer cells by inhibiting the activation of the PI3K/AKT signaling pathway. HMGA2, a downstream target gene of let-7, exhibits high expression in oral cancer. However, overexpression of HMGA2 diminishes the inhibitory effects induced by let-7 overexpression on the proliferation, migration, and invasion of oral cancer cells. The occurrence and progression of oral cancer cells are inhibited by Let-7 through the downregulation of HMGA2, potentially mediated by the inhibition of PI3K/AKT signaling pathway activation.

Astragaloside IV inhibits the proliferation, migration, invasion, and epithelial-mesenchymal transition of oral cancer cells by aggravating autophagy

Oral cancer is one usual tumor that sorely affects the health of people and even result into death. Astragaloside IV (AS-IV) is one of the major components of Astragalus membranaceus extract, and has been identified to exhibit ameliorative functions in some cancers. Nevertheless, the regulatory impacts and correlative pathways of AS-IV in oral cancer remain vague. In this study, it was discovered that cell growth was gradually weakened with the increased dose of AS-IV (25, 50 and 100 μM). Additionally, it was uncovered that AS-IV restrained the EMT progress in oral cancer. The cell migration and invasion abilities were both gradually alleviated after AS-IV treatment in a dose-dependent manner. Moreover, AS-IV accelerated autophagy through intensifying LC3II/LC3I level and LC3B fluorescence intensity. At last, it was clarified that AS-IV triggered the AMPK pathway and retarded the AKT/mTOR pathway. In conclusion, AS-IV restrained cell proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT) progress in oral cancer by aggravating autophagy through modulating the AMPK and AKT/mTOR pathways. This work may offer novel evidence on AS-IV in the treatment of oral cancer.

Effect of Mifepristone on Migration and Proliferation of Oral Cancer Cells.

Glucocorticoid receptor (GR) overexpression has been linked to increased tumour aggressiveness and treatment resistance. GR antagonists have been shown to enhance treatment effectiveness. Emerging research has investigated mifepristone, a GR antagonist, as an anticancer agent with limited research in the context of oral cancer. This study investigated the effect of mifepristone at micromolar (µM) concentrations of 1, 5, 10 and 20 on the proliferation and migration of oral cancer cells, at 24 and 48 h. Scratch and scatter assays were utilised to assess cell migration, MTT assays were used to measure cell proliferation, Western blotting was used to investigate the expression of GR and the activation of underlying Phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt) and mitogen-activated protein kinase (MAPK) signalling pathways, and immunofluorescence (IF) was used to determine the localisation of proteins in HaCaT (immortalised human skin keratinocytes), TYS (oral adeno squamous cell carcinoma), and SAS-H1 cells (squamous cell carcinoma of human tongue). Mifepristone resulted in a dose-dependent reduction in the proliferation of HaCaT, TYS, and SAS-H1 cells. Mifepristone at a concentration of 20 µM effectively reduced collective migration and scattering of oral cancer cells, consistent with the suppression of the PI3K-Akt and MAPK signalling pathways, and reduced expression of N-Cadherin. An elongated cell morphology was, however, observed, which may be linked to the localisation pattern of E-Cadherin in response to mifepristone. Overall, this study found that a high concentration of mifepristone was effective in the suppression of migration and proliferation of oral cancer cells via the inhibition of PI3K-Akt and MAPK signalling pathways. Further investigation is needed to define its impact on epithelial-mesenchymal transition (EMT) markers.

Anticancer potential of thiocolchicoside and lauric acid loaded chitosan nanogel against oral cancer cell lines: a comprehensive study

The present study explored the anticancer activity of a Chitosan-based nanogel incorporating thiocolchicoside and lauric acid (CTL) against oral cancer cell lines (KB-1). Cell viability, AO/EtBr dual staining and Cell cycle analysis were done to evaluate the impact of CTL nanogel on oral cancer cells. Real-time PCR was performed to analyze proapoptotic and antiapoptotic gene expression in CTL-treated KB-1 cells. Further, molecular docking analysis was conducted to explore the interaction of our key ingredient, thiocolchicoside and its binding affinities. The CTL nanogel demonstrated potent anticancer activity by inhibiting oral cancer cell proliferation and inducing cell cycle arrest in cancer cells. Gene expression analysis indicated alterations in Bax and Bcl-2 genes; CTL nanogel treatment increased Bax mRNA expression and inhibited the Bcl-2 mRNA expression, which showed potential mechanisms of the CTL nanogel's anticancer action. It was found that thiocolchicoside can stabilize the protein's function or restore it as a tumour suppressor. The CTL nanogel exhibited excellent cytotoxicity and potent anticancer effects, making it a potential candidate for non-toxic chemotherapy in cancer nanomedicine. Furthermore, the nanogel's ability to modulate proapoptotic gene expression highlights its potential for targeted cancer therapy. This research contributes to the growing interest in Chitosan-based nanogels and their potential applications in cancer treatment.

GPD1 relieves the proliferation, migration and invasion abilities of oral cancer cells by inhibiting mitochondrial function

GPD1 relieves the proliferation, migration and invasion abilities of oral cancer cells by inhibiting mitochondrial function

SLC2A3 promotes tumor progression through lactic acid-promoted TGF-β signaling pathway in oral squamous cell carcinoma.

Oral squamous cell carcinoma is a malignant tumor of the head and neck, and its molecular mechanism remains to be explored. By analyzing the OSCC data from the TCGA database, we found that SLC2A3 is highly expressed in OSCC patients. The expression level of SLC2A3 was verified by RT-PCR and western blotting in OSCC cell lines. The function of SLC2A3 in OSCC cell lines and Lactic acid in SLC2A3-knockdown OSCC cells were detected by colony formation, CCK8, transwell, and wound healing assays. The effect of SLC2A3 on tumor growth and metastasis was tested in vivo. GSEA and Western blot were used to analyze and validate tumor phenotypes and signaling pathway molecules. We analyzed OSCC datasets in the TCGA database and found that SLC2A3 had abnormally high expression and was associated with poor prognosis. We also found that oral squamous cell carcinoma cells had increased proliferation, migration, invasion, EMT phenotype, and glycolysis due to SLC2A3 overexpression. Conversely, SLC2A3 knockdown had the opposite effect. Our in vivo experiments confirmed that SLC2A3 overexpression promoted tumor growth and metastasis while knockdown inhibited it. We also observed that high SLC2A3 expression led to EMT and the activation of the TGF-β signaling pathway, while knockdown inhibited it. Interestingly, exogenous lactic acid restored the EMT, proliferation, migration, and invasion abilities of oral cancer cells inhibited by knocking down SLC2A3. Our study reveals that SLC2A3 expression was up-regulated in OSCC. SLC2A3 activates the TGF-β signaling pathway through lactic acid generated from glycolysis, thus regulating the biological behavior of OSCC.

Advances in Small Molecular Agents against Oral Cancer.

Oral cancer is a common malignancy with a high mortality rate. Although surgery is the best treatment option for patients with cancer, this approach is ineffective for advanced metastases. Molecular agents are irreplaceable in preventing and treating distant metastases. This review aims to summarise the molecular agents used for the treatment of oral cancer in the last decade and describe their sources and curative effects. These agents are classified into phenols, isothiocyanates, anthraquinones, statins, flavonoids, terpenoids, and steroids. The mechanisms of action of these agents include regulating the expression of cell signalling pathways and related proteases to affect the proliferation, autophagy, migration, apoptosis, and other biological aspects of oral cancer cells. This paper may serve as a reference for subsequent studies on the treatment of oral cancer.

Oral Malignant Burkitt’s Lymphoma and It’s Problems

A non-Hodgkin lymphoma with rapid growth and aggressive behavior is Burkitt's lymphoma. Burkitt's lymphoma (BL) is also an oral cancer of lymphoid origin with a high percentage of occurrences and includes an advanced B-cell neoplasm. Fundamentally, the exact cause of BL is unknown. This disease commonly occurs in people with weakened immune systems or children related to the Epstein-Barr virus (EBV) and chronic malaria. Burkitt lymphoma can be fatal. Burkitt lymphoma is a rare but highly aggressive (fast-growing) B-cell non-Hodgkin lymphoma (NHL). This disease may affect the jaw, central nervous system, bowel, kidneys, ovaries, or other organs Cancer cells in BL can spread to all parts of the body. Inhibiting the proliferation of BL oral cancer cells requires a viable and efficient plan. One of them is using medicinal plants whose antitumor potential needs to be scientifically tested. However, Burkitt lymphoma is often very responsive to the currently recommended intensive chemotherapy regimens, and cure rates for this disease remain high. Studies show people who receive treatment right away have high rates of remission, meaning after treatment they don’t have symptoms or signs of the condition. The aim of this review is to discuss Burkitt's lymphoma (BL) in diagnosis and treatment. Burkitt's lymphoma, or Raji cell, is a B-cell non-Hodgkin lymphoma that is very aggressive

Anti-oral cancer properties of potential probiotic lactobacilli isolated from traditional milk, cheese, and yogurt

This study investigates the probiotic and anti-cancer effects of 21 isolated Lactobacillus strains from cheese, milk, and yogurt in Kermanshah, Iran, on oral cancer cell lines KB and OSCC. Four selected isolates (Y33, M45, C5, and C28) displayed good viability and resistance to specific antibiotics. Notably, strains C28 and Y33 exhibited the best results, showing susceptibility or semi-susceptibility to five antibiotics. Y33, with high cell surface hydrophobicity (62%), demonstrated significant anti-pathogenic activity, inhibiting the growth of tested pathogens and displaying strong adhesion to human intestinal Caco-2 cells (52%). Further assessments, including acridine orange/ethidium bromide staining and mRNA expression analysis, revealed four isolates (C5, C28, M45, and Y33) with promising probiotic properties. Particularly, Y33’s protein-based extract metabolites showed dose- and time-dependent inhibition of KB and OSCC cancer cell lines, inducing apoptosis without significant cytotoxic effects on normal cells. Y33 (Lactiplantibacillus plantarum) exhibited the strongest probiotic potential, surpassing conventional anti-cancer drugs, suggesting its therapeutic potential for preventing oral cancer cell proliferation and improving survival rates in oral cancer patients.

Michelia compressa-Derived Santamarine Inhibits Oral Cancer Cell Proliferation via Oxidative Stress-Mediated Apoptosis and DNA Damage.

The anti-oral cancer effects of santamarine (SAMA), a Michelia compressa var. compressa-derived natural product, remain unclear. This study investigates the anticancer effects and acting mechanism of SAMA against oral cancer (OC-2 and HSC-3) in parallel with normal (Smulow-Glickman; S-G) cells. SAMA selectively inhibits oral cancer cell viability more than normal cells, reverted by the oxidative stress remover N-acetylcysteine (NAC). The evidence of oxidative stress generation, such as the induction of reactive oxygen species (ROS) and mitochondrial superoxide and the depletion of mitochondrial membrane potential and glutathione, further supports this ROS-dependent selective antiproliferation. SAMA arrests oral cancer cells at the G2/M phase. SAMA triggers apoptosis (annexin V) in oral cancer cells and activates caspases 3, 8, and 9. SAMA enhances two types of DNA damage in oral cancer cells, such as γH2AX and 8-hydroxy-2-deoxyguanosine. Moreover, all of these anticancer mechanisms of SAMA are more highly expressed in oral cancer cells than in normal cells in concentration and time course experiments. These above changes are attenuated by NAC, suggesting that SAMA exerts mechanisms of selective antiproliferation that depend on oxidative stress while maintaining minimal cytotoxicity to normal cells.

POLE2 Regulates Apoptosis of Oral Squamous Cell Carcinoma Cells through the PI3K/AKT Signaling Pathway.

Oral squamous cell carcinoma (OSCC) is the most common malignant tumor of the head and neck, but its occurrence and progression mechanisms remain unclear. In addition-there is a lack of effective targeting drugs. The second major subunit of DNA polymerase (POLE2) catalyzes the prolongation of new strand replication and modifies exonuclease domain activity. Our previous study found that POLE2 was associated with OSCC progression, but the mechanism remains unclear. The expression of POLE2 in OSCC tissues was detected using immunological assays. Mann-Whitney U analysis was used to investigate the relationship between POLE2 gene expression and tumor classification and prognosis of OSCC. POLE2 expression was inhibited in OSCC cells, and the effects of gene and protein expression were detected using RT-PCR and Western blotting. The POLE2 knockout model was constructed by transfecting a lentiviral vector. Cell proliferation, apoptosis, and migration were detected using various assays including colony formation, MTT, flow cytometry, wound healing assay, Transwell assay, and the Human Apoptosis Antibody Array. The animal model of OSCC was established by subcutaneous injection of transfected HN6 into 4-week-old female nude mice. After 30 days, tumors were removed under anesthesia and tumor weight and dimension were recorded. Tumor cell proliferation was analyzed using Ki67 staining. POLE2 gene levels were significantly higher in the OSCC tissues than in the normal tissues. In addition, POLE2 gene levels were statistically correlated with tumor classification and prognosis. Silencing POLE2 inhibited the proliferation of oral cancer cells and promoted apoptosis in vitro. Animal experiments also supported a positive correlation between POLE2 and OSCC tumor formation. We further demonstrated that POLE2 could upregulate the expression of apoptosis-related proteins such as caspase-3, CD40, CD40L, DR6, Fas, IGFBP-6, p21, and SMAC. In addition, POLE2 regulated OSCC development by inhibiting the PI3K/AKT signaling pathway. POLE2 is closely related to the progression of OSCC. Thus, POLE2 may be a potential target for OSCC treatment.

Expression and gene regulatory network of S100A16 protein in cervical cancer cells based on data mining

S100A16 protein belongs to the S100 family of calcium-binding proteins, which is widely distributed in human tissues and highly conserved. S100 calcium-binding proteins possess broad biological functions, such as cancer cell proliferation, apoptosis, tumor metastasis, and inflammation (Nat Rev Cancer 15:96–109, 2015). The S100A16 protein was initially isolated from a cell line derived from astrocytoma. The S100A16 protein, consisting of 103 amino acids, is a small acidic protein with a molecular weight of 11,801.4 Da and an isoelectric point (pI) of 6.28 (Biochem Biophys Res Commun 313:237–244, 2004). This protein exhibits high conservation among mammals and is widely expressed in various human tissues (Biochem Biophys Res Commun 322:1111–1122, 2004). Like other S100 proteins, S100A16 contains two EF-hand motifs that form a helix-loop-helix structural domain. The N-terminal domain and the C-terminal domain of S100A16 are connected by a "hinge" linker.S100A16 protein exhibits distinct characteristics that distinguish it from other S100 proteins. A notable feature is the presence of a single functional Ca2 + binding site located in the C-terminal EF-hand, consisting of 12 amino acids per protein monomer (J Biol Chem 281:38905–38917, 2006). In contrast, the N-terminal EF-hand of S100A16 comprises 15 amino acids instead of the typical 14, and it lacks the conserved glutamate residue at the final position. This unique attribute may contribute to the impaired Ca2 + binding capability in the N-terminal region (J Biol Chem 281:38905–38917, 2006). Studies have shown an integral role of S100 calcium-binding proteins in the diagnosis, treatment, and prognosis of certain diseases (Cancers 12:2037, 2020). Abnormal expression of S100A16 protein is implicated in the progression of breast and prostate cancer, but an inhibitor of oral cancer and acute lymphoblastic leukemia tumor cell proliferation (BMC Cancer 15:53, 2015; BMC Cancer 15:631, 2015). Tu et al. (Front Cell Dev Biol 9:645641, 2021) indicate that the overexpression of S100A16 mRNA in cervical cancer(CC) such as cervical squamous cell carcinoma and endocervical adenocarcinoma as compared to the control specimens. Tomiyama N. and co-workers (Oncol Lett 15:9929–9933, 2018) (Tomiyama, N) investigated the role of S100A16 in cancer stem cells using Yumoto cells (a CC cell line),The authors found upregulation of S100A16 in Yumoto cells following sphere formation as compared to monolayer culture.Despite a certain degree of understanding, the exact biological function of S100A16 in CC is still unclear. This article explores the role of S100A16 in CC through a bioinformatics analysis. Referencing the mRNA expression and SNP data of cervical cancer available through The Cancer Genome Atlas (TCGA) database, we analyzed S100A16 and its associated regulatory gene expression network in cervical cancer. We further screened genes co-expressed with S100A16 to hypothesize their function and relationship to the S100A16 cervical cancer phenotype.Our results showed that data mining can effectively elucidate the expression and gene regulatory network of S100A16 in cervical cancer, laying the foundation for further investigations into S100A16 cervical tumorigenesis.

Inhibition of transforming growth factor-β signals suppresses tumor formation by regulation of tumor microenvironment networks.

The tumor microenvironment (TME) consists of cancer cells surrounded by stromal components including tumor vessels. Transforming growth factor-β (TGF-β) promotes tumor progression by inducing epithelial-mesenchymal transition (EMT) in cancer cells and stimulating tumor angiogenesis in the tumor stroma. We previously developed an Fc chimeric TGF-β receptor containing both TGF-β type I (TβRI) and type II (TβRII) receptors (TβRI-TβRII-Fc), which trapped all TGF-β isoforms and suppressed tumor growth. However, the precise mechanisms underlying this action have not yet been elucidated. In the present study, we showed that the recombinant TβRI-TβRII-Fc protein effectively suppressed invitro EMT of oral cancer cells and invivo tumor growth in a human oral cancer cell xenograft mouse model. Tumor cell proliferation and angiogenesis were suppressed in tumors treated with TβRI-TβRII-Fc. Molecular profiling of human cancer cells and mouse stroma revealed that K-Ras signaling and angiogenesis were suppressed. Administration of TβRI-TβRII-Fc protein decreased the expression of heparin-binding epidermal growth factor-like growth factor (HB-EGF), interleukin-1β (IL-1β) and epiregulin (EREG) in the TME of oral cancer tumor xenografts. HB-EGF increased proliferation of human oral cancer cells and mouse endothelial cells by activating ERK1/2 phosphorylation. HB-EGF also promoted oral cancer cell-derived tumor formation by enhancing cancer cell proliferation and tumor angiogenesis. In addition, increased expressions of IL-1β and EREG in oral cancer cells significantly enhanced tumor formation. These results suggest that TGF-β signaling in the TME controls cancer cell proliferation and angiogenesis by activating HB-EGF/IL-1β/EREG pathways and that TβRI-TβRII-Fc protein is a promising tool for targeting the TME networks.

α-Mangostin and lawsone methyl ether in tooth gel synergistically increase its antimicrobial and antibiofilm formation effects in vitro

Objectivesα-Mangostin (α-MG) and lawsone methyl ether (LME) show antimicrobial and anti-biofilm activities. The objectives of this study were to develop a herbal tooth gel containing α-MG and LME plus fluoride and determine its antimicrobial, anti-biofilm formation, anti-cancer, anti-inflammatory, wound healing, and enamel microhardness effects.MethodsAntimicrobial assays against Streptococcus mutans, Porphyromonas gingivalis, and Candida albicans were performed. The microbes’ ultrastructural morphology was assessed using Transmission Electron Microscopy. The effect on microbial biofilm formation was tested by a broth microdilution. Cell viability was assessed with MTT assay. The anti-inflammatory effect was investigated by measuring inhibition of nitric oxide production. Enamel microhardness was measured via Vickers microhardness testing. The enamel chemical composition was investigated with Fourier Transform Spectrometer. The enamel surface morphology and fluoride content were examined by Scanning Electron Microscopy and Energy Dispersive X-ray Spectroscopy.ResultsThe results show synergistic effects of α-MG and LME on antimicrobial activity and antibiofilm formation without cytotoxicity at a therapeutic dose. At a higher dose, the tooth gel inhibited proliferation of cancer cell line. Enamel microhardness was increased after brushing with the tooth gel plus fluoride. A large amount of fluoride was detected on the enamel surface.ConclusionThe tooth gel containing α-MG and LME synergized its antimicrobial activity and antibiofilm formation and inhibited oral cancer cell proliferation. Incorporating fluoride into the tooth gel increased enamel microhardness. Thus, the herbal tooth gel containing α-MG and LME plus fluoride may be useful for preventing dental caries and promoting oral health.

Demethoxymurrapanine, an indole-naphthoquinone alkaloid, inhibits the proliferation of oral cancer cells without major side effects on normal cells.

Antioral cancer drugs need a greater antiproliferative impact on cancer than on normal cells. Demethoxymurrapanine (DEMU) inhibits proliferation in several cancer cells, but an in-depth investigation was necessary. This study evaluated the proliferation-modulating effects of DEMU, focusing on oral cancer and normal cells. DEMU (0, 2, 3, and 4 μg/mL) at 48 h treatments inhibited the proliferation of oral cancer cells (the cell viability (%) for Ca9-22 cells was 100.0 ± 2.2, 75.4 ± 5.6, 26.0 ± 3.8, and 15.4 ± 1.4, and for CAL 27 cells was 100.0 ± 9.4, 77.2 ± 5.9, 57.4 ± 10.7, and 27.1 ± 1.1) more strongly than that of normal cells (the cell viability (%) for S-G cells was 100.0 ± 6.6, 91.0 ± 4.6, 95.0 ± 2.6, and 95.8 ± 5.5), although this was blocked by the antioxidant N-acetylcysteine. The presence of oxidative stress was evidenced by the increase of reactive oxygen species and mitochondrial superoxide and the downregulation of the cellular antioxidant glutathione in oral cancer cells, but these changes were minor in normal cells. DEMU also caused greater induction of the subG1 phase, extrinsic and intrinsic apoptosis (annexin V and caspases 3, 8, and 9), and DNA damage (γH2AX and 8-hydroxy-2-deoxyguanosine) in oral cancer than in normal cells. N-acetylcysteine attenuated all these DEMU-induced changes. Together, these data demonstrate the preferential antiproliferative function of DEMU in oral cancer cells, with the preferential induction of oxidative stress, apoptosis, and DNA damage in these cancer cells, and low cytotoxicity toward normal cells.

Silencing POLE2 promotes apoptosis and inhibits proliferation of oral squamous cell carcinomas by inhibiting PI3K/AKT signaling pathway.

Oral squamous cell carcinoma is the most common malignant tumor in the head and neck at present, but the mechanism of its occurrence and development is still unclear, and there is still a lack of effective targeting drugs. The second major subunit of DNA polymerase (POLE2) has exonuclease activity and can catalyze the replication and modification of new chains. Our previous studies have found that it is associated with OSCC progression, but the mechanism is unclear.The expression of POLE2 in OSCC was detected by immunological method. The expression of POLE2 was inhibited in OSCC cells, and the biological function of the cells was detected by RT-PCR and Western Blot. Cell proliferation, apoptosis and migration were detected by colony formation, MTT, flow cytometry, wound healing and Transwell. The expression level of POLE2 gene in OSCC was significantly higher than that in normal tissues. In addition, the expression level of POLE2 gene was significantly different from the tumor type and prognosis. During the development of oral squamous cell carcinoma, silencing POLE2 inhibits the proliferation of oral cancer cells and promotes apoptosis. The results of animal experiments also support the positive correlation between POLE2 and OSCC progression. We further demonstrated that POLE2 can up-regulate the downregulation of apoptosis-related proteins such as Caspase3, CD40, CD40L, DR6, Fas, IGFBP-6, P21, and SMAC. In addition, POLE2 regulates OSCC progression by inhibiting the PI3K/AKT pathway. POLE2 is closely related to the progression of OSCC, and POLE2 may be a potential target for OSCC treatment.

Synergistic Effects of New Curcumin Analog (PAC) and Cisplatin on Oral Cancer Therapy.

Oral cancer has traditionally been treated with surgery, radiotherapy, chemotherapy, or a combination of these therapies. Although cisplatin, a chemotherapy drug, can effectively kill oral cancer cells by forming DNA adducts, its clinical use is limited due to adverse effects and chemo-resistance. Therefore, there is a need to develop new, targeted anticancer drugs to complement chemotherapy, allowing for reduced cisplatin doses and minimizing adverse effects. Recent studies have shown that 3,5-Bis (4-hydroxy-3-methoxybenzylidene)-N-methyl-4-piperidine (PAC), a new curcumin analog, possesses anticancer properties and could be considered a complementary or alternative therapy. In this study, we aimed to assess the potential complementary effects of PAC in combination with cisplatin for treating oral cancer. We conducted experiments using oral cancer cell lines (Ca9-22) treated with different concentrations of cisplatin (ranging from 0.1 μM to 1 μM), either alone or in conjunction with PAC (2.5 and 5 μM). Cell growth was measured using the MTT assay, while cell cytotoxicity was evaluated using an LDH assay. Propidium iodide and annexin V staining were employed to examine the impact on cell apoptosis. Flow cytometry was used to investigate the effects of the PAC/cisplatin combination on cancer cell autophagy, oxidative stress, and DNA damage. Additionally, a Western Blot analysis was performed to assess the influence of this combination on pro-carcinogenic proteins involved in various signaling pathways. The results demonstrated that PAC enhanced the efficacy of cisplatin in a dose-dependent manner, leading to a significant inhibition of oral cancer cell proliferation. Importantly, treatment with PAC (5 μM) alongside different concentrations of cisplatin reduced the IC50 of cisplatin tenfold. Combining these two agents increased apoptosis by further inducing caspase activity. In addition, the concomitant use of PAC and cisplatin enhances oral cancer cell autophagy, ROS, and MitoSOX production. However, combined PAC with cisplatin inhibits the mitochondrial membrane potential (ΔΨm), which is a marker for cell viability. Finally, this combination further enhances the inhibition of oral cancer cell migration via the inhibition of epithelial-to-mesenchymal transition genes, such as E-cadherin. We demonstrated that the combination of PAC and cisplatin markedly enhanced oral cancer cell death by inducing apoptosis, autophagy, and oxidative stress. The data presented indicate that PAC has the potential to serve as a powerful complementary agent to cisplatin in the treatment of gingival squamous cell carcinomas.

Effects of cancer-associated fibroblasts deletion using HSVtk suicide system in OSCC.

To evaluate the biological characteristics of oral cancer cells co-cultured with cancer-associated fibroblasts (CAFs)-HSVtk and to assess the reliability of the CAFs-HSVtk suicide system in a co-culture model. CAFs were lentivirus-transfected with PCDH-HSVtk. Ganciclovir (GCV) was added and the survival rates of the CAFs-HSVtk were measured. In parallel with the selective elimination of CAFs, comparison was made of the effects of CAF-HSVtk on tumor cell proliferation/migration in a CAFs-tumor co-cultural system. Cell death of co-cultured oral cancer cells was evaluated by flow cytometry. Q-PCR analysis showed that the expression of HSVtk in the CAFs-HSVtk group was significantly higher than in the control group (p < 0.01). The survival rates of CAFs-HSVtk with GCV were significantly reduced (p < 0.01). Following selective depletion of CAFs-HSVtk, the growth and migration rates of oral cancer cells co-cultured with CAFs-HSVtk were reduced in a mixture ratio of 1:2 (p < 0.01, p < 0.01). Enhanced proliferation and migration rates of oral cancer cells in co-culture were seriously impaired after deleting CAFs using the HSVtk suicide system, while oral tumor cell death was not affected. Therefore, CAFs-HSVtk can be utilized as a valid model for CAF signature identification.

MYO1B as a prognostic biomarker and a therapeutic target in Arecoline-associated oral carcinoma.

Arecoline, the main component of betel nut, induces malignant transformation of oral cells through complicated unclear mechanisms. Thus, we aimed to screen the key genes involved in Arecoline-induced oral cancer and further verify their expressions and roles. This study included a data-mining part, a bioinformatics verification part, and an experimental verification one. First, the key gene related to oral cancer induced by Arecoline was screened. Then, the expression and clinical significance of the key gene in head and neck/oral cancer tissues were verified, and its downstream mechanisms of action were explored. Afterwards, the expression and roles of the key gene were verified by experiments at the histological and cytological levels. MYO1B was identified as the key gene. Overexpression of MYO1B was associated with lymph node metastasis and unfavorable outcomes in oral cancer. MYO1B may be mainly related to metastasis, angiogenesis, hypoxia, and differentiation. A positive correlation between MYO1B and the infiltration of macrophages, B cells, and dendritic cells was presented. MYO1B might have a close relationship with SMAD3, which may be enriched in the Wnt signaling pathway. MYO1B suppression markedly inhibited the proliferation, invasion, and metastasis abilities of both Arecoline-transformed oral cells and oral cancer cells. This study revealed MYO1B as a key gene in Arecoline-induced oral tumorigenesis. MYO1B might be a novel prognostic indicator and therapeutic target for oral cancer.

CXCL1 promoted the migration and invasion abilities of oral cancer cells and might serve as a promising marker of prognosis in tongue cancer.

Oral tongue squamous cell carcinoma tends to metastasize to cervical lymphatic nodes early which leads to a 50% drop of survival rate. CXCL1 could be secreted by LNMTca8113 cell induced lymphatic endothelial cells and promoted LNMTca8113 cell migration. The current study aimed to further explore the effect of CXCL1 on the proliferation and migration abilities of tongue cancer cells and the prognostic value of serum CXCL1 in oral tongue squamous cell carcinoma. Cell proliferation and migration ability were analysed by CCK8 assays and transwell migration assays. Immunofluorescence technique was used to show cytoskeleton. GST pull-down assay was applied to quantify the activation of GTPases. Blood samples of patients were collected and clinicopathological characteristics were analysed. CXCL1 could promote cancer cell proliferation in appropriate concentration by PI3K/AKT pathway. It also regulated the activation of Rho GTPases to mediate the rearrangements of cytoskeleton to promote tumour cell migration. Level of plasma CXCL1 could predict the possibility of early lymphatic metastasis and had a predictive value in progression-free survival and overall survival. CXCL1 could promote oral cancer cell proliferation, migration and invasion in vitro and contributed theoretical knowledge for the target selection in molecular targeted therapy. Level of plasma CXCL1 might serve as a biomarker for prognosis in oral tongue squamous cell carcinoma patients.