Inhibited Cell Migration Research Articles

Identifying CSNK1E as a therapeutic target in thyroid cancer among the core circadian clock genes.

Previous studies have shown that thyroid malignancies can alter the transcriptional oscillations of circadian clock genes. In this study, we screened the expression of core circadian clock genes in thyroid neoplasms and found that CSNK1E, NPAS2, and TIMELESS were upregulated, while ARNTL, CRY1, CRY2, PER2, and RORA were downregulated during the progression and dedifferentiation of thyroid cancer. Immunohistochemical analysis further confirmed an increase in CSNK1E expression parallel to the loss of tumor differentiation. To investigate the potential therapeutic implications, we treated thyroid cancer cell lines with two different CSNK1E inhibitors: PF670462 and IC261. Both inhibitors resulted in growth inhibition in monolayer and three-dimensional spheroid cultures. This growth inhibition was accompanied by G2/M cell cycle arrest and a decrease in CDK4 and cyclin D1 expression. Moreover, CSNK1E inhibitors suppressed cell migration and invasion and reduced the expression of epithelial-mesenchymal transition markers. In vivo experiments using xenograft models showed that the administration of IC261 significantly restrained tumor growth and decreased the Ki-67 index of the xenograft tumors. In conclusion, our study provides evidence of aberrant CSNK1E expression in thyroid cancer dedifferentiation and highlights the potential therapeutic value of targeting CSNK1E.

CircICMT upregulates and suppresses the malignant behavior of bladder cancer.

Circular RNA (circRNA) is a new type of endogenous single-stranded RNA with a covalently closed circular structure. Increasing evidence shows that circRNA plays an important role in regulating gene expression in tumors. circICMT is a circular RNA produced by the ICMT gene. Currently, the molecular function of circICMT in bladder cancer remains unclear. Differentially expressed circRNAs were identified from RNA sequencing data and circICMT was identified as a new candidate circRNA. qRT-PCR and sanger sequencing were used to detect the expression of circICMT in bladder cancer tissue specimens. Stable cell lines overexpressing and knocking down circICMT were constructed to explore the effect of circICMT on bladder cancer cells. Its biological effects were detected through wound healing experiments, colony formation experiments, CCK-8 experiments and xenogeneic tumorigenesis experiments. This study found that circICMT was significantly upregulated in bladder cancer tissue specimens. Overexpression of circICMT can inhibit cell migration, proliferation and colony formation ability, while knockdown of circICMT promotes the malignant phenotype of bladder cancer cells. Bioinformatics predictions have found that circICMT can bind to a variety of miRNAs and RBPs and may form a complex regulatory network to regulate the progression of bladder cancer. circICMT is significantly highly expressed in bladder cancer, and intervening circICMT expression affects the malignant phenotype of bladder cancer cells in vivo and in vitro, which may provide potential biomarkers and therapeutic targets for the management of bladder cancer.

The role and molecular mechanism of GDF5 in regulating cell migration and angiogenesis via the Hippo-YAP signaling pathway in colorectal cancer.

292 Background: Distant metastasis is a leading cause of poor prognosis and mortality in colorectal cancer (CRC) patients, with angiogenesis playing a crucial role in tumor progression. The TGF-β superfamily has been shown to significantly influence tumor angiogenesis, yet the biological function and molecular mechanism of Growth Differentiation Factor 5 (GDF5), a member of this superfamily, remain unexplored in CRC. Given that the efficacy of current anti-angiogenic therapies is limited to a subset of patients, identifying new therapeutic targets involved in tumor angiogenesis is of great clinical importance. GDF5, with its potential role in angiogenesis regulation, presents a promising candidate to bridge this therapeutic gap. Methods: In this study, we analyzed GDF5 expression in CRC tissue samples using both the TCGA dataset and samples from our center, revealing significantly lower GDF5 expression in tumors compared to adjacent normal tissues. Moreover, GDF5 downregulation correlated with lymph node metastasis and disease recurrence. Functional assays in vitro demonstrated that GDF5 overexpression reduced tumor cell migration and invasion, while its knockdown produced the opposite effect. Co-culture assays showed that GDF5 knockdown significantly enhanced endothelial cell migration and angiogenesis, whereas overexpression diminished these effects. Additionally, F-actin cytoskeletal staining indicated that GDF5 overexpression led to cytoskeletal remodeling in endothelial cells. Mechanistically, we found that GDF5 overexpression in tumor cells downregulated the epithelial-mesenchymal transition (EMT) marker Slug and upregulated E-cadherin, while downregulating N-cadherin. In endothelial cells, GDF5 inhibited the Hippo-YAP signaling pathway, increasing YAP phosphorylation and reducing nuclear YAP levels. Conversely, GDF5 knockdown suppressed YAP phosphorylation and promoted its nuclear translocation. Results: Our findings demonstrate that GDF5 functions as a tumor suppressor in CRC by regulating cell migration and angiogenesis. This study reveals that GDF5 exerts its anti-cancer effects by modulating both EMT in tumor cells and cytoskeletal changes in endothelial cells, leading to the inhibition of the Hippo-YAP signaling pathway and reduced angiogenic potential. These results identify GDF5 as a promising new target for anti-angiogenic therapy in CRC, offering potential avenues for improving treatment strategies in patients resistant to current therapies. Conclusions: GDF5 acts as a tumor suppressor in colorectal cancer by inhibiting cell migration and angiogenesis through modulation of the Hippo-YAP signaling pathway, making it a promising therapeutic target for anti-angiogenic treatment in patients resistant to current therapies.

Anticancer and therapeutic efficacy of XPO1 inhibition in pancreatic ductal adenocarcinoma through DNA damage and modulation of miR-193b/KRAS/LAMC2/ERK/AKT signaling cascade.

Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive and grave malignancies with confined and ineffective therapeutic options. XPO1 is a critical regulator of nuclear export and activation of tumor suppressor proteins. The present study evaluated the therapeutic potential and molecular mechanisms of XPO1 inhibition against PDAC. Firstly, we observed significant overexpression of XPO1 transcript in 179 PDAC patients than 171 normal pancreatic tissues in TCGA transcriptomic dataset. Higher XPO1 transcript levels displayed worse overall and disease-free survival. Further, we confirmed significant upregulation of XPO1 in a panel of PDAC cells. Eltanexor treatment resulted in significant inhibition of cell viability, clonogenic growth, migration, and epithelial-mesenchymal transition (EMT), along with the induction of cell cycle arrest. Mechanistically, eltanexor modulated the expression of key proteins including p21, p27, p53, cyclin B1, cyclin D1, c-Myc, N-cadherin, vimentin, E-cadherin associated with the cell viability, growth, cell cycle and EMT. Additionally, the eltanexor treatment resulted in marked increase in expression of γH2AX, and cleaved PARP, cleaved caspase-9 leading to induction of DNA damage and apoptosis of PDAC cells, respectively. Moreover, eltanexor treatment regulated the expression of key non-coding RNAs including miR193b, DINO, MALAT-1, H19, and SOX21-AS1 linked with tumorigenesis. Our results revealed a correlation among miR193b/KRAS/LAMC2, XPO1/KRAS, and LAMC2/KRAS. The findings also revealed that eltanexor treatment rescued the expression of miR193b which acts as a sponge for LAMC2 and KRAS resulting in the suppression of AKT/ERK downstream signaling cascade in PDAC. Interestingly, the combination of eltanexor with gemcitabine showed significant anticancer activity in PDAC cells. Altogether, our findings revealed the crucial role of XPO1 in modulating the expression of oncogenic proteins, ncRNAs, and DNA damage during PDAC progression as well as identified novel therapeutic miR-193b/KRAS/LAMC2/ERK/AKT axis.

A new NCL-targeting aptamer-drug conjugate as a promising therapy against esophageal cancer

Esophageal cancer (EC) is one of the most common highly malignant tumors of the digestive system, with a poor prognosis under current treatment regimens. Nucleolin (NCL) is overexpressed in many tumors, and drugs specifically targeting NCL may offer a promising strategy for treating esophageal cancer. Here, we designed and prepared a novel aptamer-conjugated drug targeting NCL by AS1411 aptamer-human serum albumin (HSA)-the apoprotein of lidamycin (LDP)-active enediyne chromophore (AE), in order to achieve targeted treatment of esophageal cancer. The experimental results revealed that AS1411-HSA-LDP effectively binds to esophageal cancer cells and could be efficiently internalized by esophageal cancer cells. In the KYSE520 xenograft tumor nude mouse model, AS1411-HSA-LDP could be targeted and enriched in the tumor location for a long time. AS1411-HSA-LDP-AE exhibited a strong cell-killing activity in esophageal cancer cells, inhibited cell migration and invasion, and induced cell apoptosis. The animal studies confirmed that AS1411-HSA-LDP-AE exhibited a strong anti-tumor effect. These findings suggested that the novel NCL-targeting aptamer-drug conjugate constructed based on lidamycin exhibited a strong anti-tumor effect, providing a promising strategy for the targeted treatment of esophageal cancer.

Synergistic Anticancer Activity of Quercetin Combined with Luteolin in MCF-7 Breast Cancer Cells via Induction of Apoptosis

Cancer is a major public health problem with its increasing incidence and mortality. The striking role of phytochemicals in the prevention and treatment of cancer is undeniable in studies. In this study, the effects of the combination of quercetin (QUR) and luteolin (LTN) on the MCF-7 human breast cancer cell line were investigated in vitro. WST-1 cell cytotoxicity assay was used to determine cytotoxic activity. The effects on colony survival and cell migration were determined by clonogenic assay and wound scratch assay, respectively. For the determination of apoptosis, AO/EB dual staining, and Caspase-3 ELISA analysis, and genomic analyses revealing p53, Bcl-2, and Bax expression levels were performed. As a result of the analyses, it was seen that especially QUR plus LTN treatment exhibited a great cytotoxic activity in cells. It was determined that the combination treatment suppressed colony survival and significantly inhibited cell migration. Quantitative analysis results show that QUR+LTN treatment triggers cellular apoptosis by upregulating Caspase-3, p53, and Bax, and downregulating Bcl-2. Supporting these findings with further in vitro and in vivo analyses may contribute significantly to revealing the promising efficacy of combined phytochemical treatment approaches on cancer.

Convergent flow-mediated mesenchymal force drives embryonic foregut constriction and splitting.

The transformation of a two-dimensional epithelial sheet into various three-dimensional structures is a critical process in generating the diversity of animal forms. Previous studies of epithelial folding have revealed diverse mechanisms driven by epithelium-intrinsic or -extrinsic forces. Yet little is known about the biomechanical basis of epithelial splitting, which involves extreme folding and eventually a topological transition breaking the epithelial tube. Here, we leverage tracheal-esophageal separation (TES), a critical and highly conserved morphogenetic event during tetrapod embryogenesis, as a model system for interrogating epithelial tube splitting both in vivo and ex vivo. Comparing TES in chick and mouse embryos, we identified an evolutionarily conserved, compressive force exerted by the mesenchyme surrounding the epithelium, as being necessary to drive epithelial constriction and splitting. The compressive force is mediated by localized convergent flow of mesenchymal cells towards the epithelium. We further found that Sonic Hedgehog (SHH) secreted by the epithelium functions as an attractive cue for mesenchymal cells. Removal of the mesenchyme, inhibition of cell migration, or loss of SHH signaling all abrogate TES, which can be rescued by externally applied pressure. These results unveil the biomechanical basis of epithelial splitting and suggest a mesenchymal origin of tracheal-esophageal birth defects.

Calothrixin B by docking JAK2 is a potential therapeutic inhibitor for pancreatic ductal adenocarcinoma.

Pancreatic cancer, a highly invasive and prognostically unfavorable malignant tumor, consistently exhibits resistance to conventional chemotherapy, leading to substantial side effects and diminished patient quality of life. This highlights the critical need for the discovery of novel, effective, and safe chemotherapy drugs. This study aimed to explore bioactive compounds, particularly natural products, as an alternative for JAK2 protein inhibitor in cancer treatment. Molecular docking, molecular dynamics, and Western blot experiments were conducted to verify the binding of Calothrixin B to JAK2 and its inhibitory effect on the JAK2-STAT3 signaling axis. Recognizing the significant impact of JAK-STAT3 signaling pathway in pancreatic cancer, we screened the Zinc database to discover potential JAK2 inhibitors, and identified the small molecule Calothrixin B as a promising drug. Molecular simulations revealed stable interactions and the formation of hydrogen bonds between Calothrixin B and specific amino acids (Asp 994, Leu 855, and Arg 980) after a 100 ns simulation. Furthermore, we show that Calothrixin B inhibited the activity of the JAK2-STAT3 signaling pathway, arrested pancreatic cancer cells in the G1 phase, induced apoptosis, and significantly inhibited cell migration. Moreover, in vivo on a subcutaneous tumor model in nude mice confirmed that Calothrixin B effectively inhibited tumor growth in nude mice. In addition, the combination of Carlothrixin B and gemcitabine had a better inhibitory effect on pancreatic cancer cells. These findings introduce new avenues for Calothrixin B as promising therapy for pancreatic cancer.

Dual ligand functionalized pH-sensitive liposomes for metastatic breast cancer treatment: in vitro and in vivo assessment.

This research demonstrates the design and development of a novel dual-targeting, pH-sensitive liposomal (pSL) formulation of 5-Fluorouracil (5-FU), i.e., (5-FU-iRGD-FA-pSL) to manage breast cancer (BC). The motivation to explore this formulation is to overcome the challenges of systemic toxicity and non-specific targeting of 5-FU, a conventional chemotherapeutic agent. The proposed formulation also combines folic acid (FA) and iRGD peptides as targeting ligands to enhance tumor cell specificity and penetration, while the pH-sensitive liposomes ensure the controlled drug release in the acidic tumor microenvironment. The physicochemical characterization revealed that 5-FU-iRGD-FA-pSL possesses optimal size, low polydispersity index, and favorable zeta potential, enhancing its stability and targeting capabilities. In vitro studies demonstrated significantly enhanced cellular uptake, cytotoxicity, and inhibition of cell migration in MCF-7 BC cells compared to free 5-FU and non-targeted liposomal formulations. DAPI staining revealed significant apoptotic features, including chromatin condensation (CC) and nuclear fragmentation (NF), with 5-FU-iRGD-FA-pSL inducing more pronounced apoptosis compared to 5-FU-pSL. Furthermore, in vivo analysis in a BC rat model showed superior anti-tumor efficacy, reduced systemic toxicity, and improved safety profile of the 5-FU-iRGD-FA-pSL formulation. This dual-targeting pSL system presents a promising approach for enhancing the therapeutic index of 5-FU, offering a potential strategy for more effective BC treatment.

Buthionine sulfoximine acts synergistically with doxorubicin as a sensitizer molecule on different tumor cell lines

ABSTRACT The chemotherapeutic drug doxorubicin (DOX) has been widely used for treating solid tumors attributed to its antiproliferative effectiveness; however, its clinical use is limited due to side effects, including cardiotoxicity, myelosuppression, and drug resistance. Combining DOX with buthionine sulfoximine (BSO), a glutathione (GSH) synthesis inhibitor, showed promising results in overcoming these adverse effects, potentially reducing the required DOX dose while maintaining efficacy. The aim of the present study was to examine the effects of different concentrations of BSO and DOX, both individually and in combination, utilizing B16/F10 (murine melanoma), SNB-19 (human glioblastoma), S180 (murine sarcoma), and SVEC4–10 (murine endothelial) cell lines. Cell viability, migration, and clonogenicity were assessed using the following assays MTT, scratch, and colony formation. Antioxidant levels of GSH, as well as activities catalase (CAT), and superoxide dismutase (SOD) were measured. BSO alone exhibited minimal cytotoxic effects, while DOX alone reduced cell viability significantly. The combination of BSO+DOX decreased IC50 values for most cell lines, demonstrating a synergistic effect, especially in B16/F10, S180, and SVEC4–10 cells. BSO+DOX combination significantly inhibited cell migration and clonogenicity compared to DOX alone. While GSH levels were decreased with BSO+DOX treatment activities of CAT and SOD increased following DOX administration but remained unchanged by BSO. These results suggest that BSO may be considered a valuable tool to improve DOX therapeutic efficacy, particularly in cases of chemotherapy-resistant tumors, as BSO enhances DOX activity while potentially reducing systemic chemotherapeutic drug toxicity.

Methanolic Leaves Extract of Ziziphus spina-christi Inhibits Cell Proliferation and Migration of HER2-Positive Breast Cancer via p38 MAPK Signaling Pathway.

Human epidermal growth factor receptor 2 (HER2) is a subtype of breast cancer that is associated with poor prognosis and low survival rates. The discovery of novel anti-cancer agents to manage this subtype of cancer is still needed. Ziziphus spina-christi (ZSC) is a plant species that is native to Qatar. It exerts various biological activities, including cytotoxicity as it contains different essential bioactive constituents, mainly rutin and quercetin. To examine the outcome of ZSC on HER2-positive breast cancer, we standardized the ZSC methanolic leaves extracted by Reverse Phase High-Performance Liquid Chromatography (RP-HPLC) analysis using the flavonoids rutin and quercetin as marker compounds. Here we used two HER2-positive breast cancer cell lines, ZR-75-1 and SK-BR-3, and the chorioallantoic membrane as an angiogenesis model. We found that ZSC extract significantly reduces viability, alters the normal morphological phenotype of HER2-positive breast cancer cells, and inhibits cell migration as well as colony formation; this is accompanied by deregulating different apoptotic markers such as Bax/Bcl-2 and NF-κB in both cell lines. Additionally, ZSC methanolic extract significantly represses the angiogenesis of the chorioallantoic membrane model. Moreover, the molecular pathway investigations pointed out that ZSC extract represses the activity of HER2 and p38 MAPK which could be the main pathways behind the effect of ZSC in HER2-positive cells. Collectively, our results support the potential role of ZSC in the management of HER2-positive breast cancer and form the basis for future investigations.

Inhibitory Effects of Different Doses of Matrine on Breast Cancer and Its Relationship with miR-188

Background Malignant tumors represented by breast cancer still have limitations in clinical treatment methods. Matrine is a compound with anticancer activity, but its inhibitory effect on breast cancer and its mechanism for regulating miR-188 are still unclear. Purpose Therefore, it is necessary to explore more effective breast cancer treatment methods and understand the intervention mechanism of matrine and its effect on miR-188. Methods A nude mouse model of breast cancer was in this study constructed and divided into a model group, 4 mg/kg group, 8 mg/kg group, drug group, and miR-188 mimic group. Different concentrations of matrine were administered intragastrically, and cell proliferation and apoptosis were observed. At the same time, a specific mechanism for miR-188 in the anti-breast cancer effect of matrine was explored by overexpressing miR-188. Results It was found that matrine inhibited the proliferation of breast cancer cells and caused cancer cell apoptosis. In addition, it inhibited cell migration in a dose-dependent manner. At the same time, miR-188 was lowly expressed in breast cancer and significantly increased after matrine treatment. Overexpression of miR-188 enhanced the antitumor effect of matrine. Phosphatase and tensin homolog (PTEN) was also activated in the surface by matrine, and expressions of matrix metalloproteinase-9 (MMP-9) and matrix metalloproteinase-2 (MMP-2) were inhibited. This study shows that matrine has a significant inhibitory effect on breast cancer, and its mechanism is related to upregulation of miR-188, activation of PTEN, and inhibition of MMP-9 and MMP-2 expressions. Conclusion miR-188 is involved in the anti-breast cancer process, which can be used as the theoretical basis of matrine potential drugs for breast cancer treatment. Meanwhile, miR-188 and matrine will also have great potential in developing new breast cancer treatment methods, which can provide ideas and a basis for further development of related studies.

Migrasome-related prognostic signature TSPAN4 correlates with immune infiltrates and metabolic disturbances in hepatocellular carcinoma.

We aim to comprehensively analyze and validate the prognostic efficacy of tetraspanin 4 (TSPAN4) and several other migrasome-related markers in hepatocellular carcinoma (HCC). The expression, diagnostic, and prognostic efficacy of five migrasome-related genes in HCC were analyzed using several databases. Five pairs of adjacent non-tumor tissues and HCC tissues were used to validate the expression. The prognostic efficacy of TSPAN4 was validated in a HCC cohort. TSPAN4 was knocked down in Huh-7 cells, EdU, and CCK-8, and wound healing assays were conducted to analyze its effects on cell proliferation and migration. In addition, transcriptomic sequencing was used to identify differentially expressed genes. Compared with those in normal tissues, four genes (TSPAN4, PIGK, NDST1, and CPQ) were elevated in liver hepatocellular carcinoma (LIHC), but not TSPAN7. Of these, only elevated TSPAN4 predicted unfavorable prognosis of HCC patients. The expression and prognostic efficacy of TSPAN4 were further confirmed in a HCC cohort (97 patients); and patients in the TSPAN4high group showed unfavorable overall survival (log-rank P = 0.0055). Functional analysis showed that TSPAN4 knockdown significantly suppressed cell migration, but not cell proliferation. Moreover, TSPAN4 knockdown induced disturbances of the metabolic pathways, mainly pentose and glucuronate interconversions. TPSAN4 is a promising prognostic and therapeutic target for HCC treatment and may be involved in the metabolic pathways that affect disease progression.

Unveiling the Anti-Angiogenic Potential of Small-Molecule (Kinase) Inhibitors for Application in Rheumatoid Arthritis.

Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by inflammation leading to joint damage and systemic complications. Angiogenesis promotes inflammation and contributes to RA progression. This study evaluated potential anti-angiogenic effects of several compounds including small-molecule kinase inhibitors, such as sunitinib (pan-kinase inhibitor), tofacitinib (JAK-inhibitor), NIKi (NF-κB-inducing kinase inhibitor), and the integrin-targeting peptide fluciclatide, using a scratch assay and 3D spheroid-based models of angiogenesis. For all drugs tested in the low micromolar range (1-25 μM), sunitinib (as positive anti-angiogenetic control) showed marked inhibition of endothelial cell (EC) migration and sprouting, effectively reducing both scratch closure and sprout formation. Tofacitinib exhibited marginal effectiveness in the scratch assay, but performed better in the 3D models (55% inhibition), whereas NIKi showed around 50% anti-angiogenic effects in both models. Fluciclatide changed EC morphology rather than migration, and only when stimulated with synovial fluid in spheroid model did it show inhibitory effects (at ≥2.5 µM), with none below this dosage. These results highlight the potential of NIKi and tofacitinib for angiogenesis inhibition and of fluciclatide for safe diagnostic targeting of microdose in RA, as well as the need for advanced screening models that mimic RA's complex inflammatory pro-angiogenic environment.

Synthesis and Characterization of Brucine Gold Nanoparticles for Targeted Breast Cancer Therapy: Mechanistic Insights Into Apoptosis and Antioxidant Disruption in MCF-7 Cells.

Globally, breast cancer continues to be the leading type of cancer affecting women, with rising mortality rates projected by 2030. This highlights the importance of developing new, affordable treatments, like drug delivery systems that use nanoparticles. Gold nanoparticles (AuNPs), including their exceptional optical and physical attributes, make them an attractive vehicle for targeted treatment, allowing for accurate and focused delivery of medication directly to cancerous cells while reducing harmful side effect. This study focuses on the synthesis and characterization of brucine-gold nanoparticles (BRU-AuNPs) for targeted breast cancer therapy by evaluating their antioxidant and apoptotic mechanism. BRU-AuNPs were synthesized and characterized (UV-Vis spectroscopy, Fourier transform infrared [FTIR], scanning electron microscopy [SEM], x-ray diffraction [XRD], dynamic light scattering [DLS], and zeta potential) to confirm successful synthesis, size, and stability. Invitro studies were assessed using MCF-7 breast cancer cell lines to evaluate cell cytotoxicity, antioxidant balance, reactive oxygen species (ROS) generation, mitochondrial membrane potential, apoptosis induction, cell migration, and pro-apoptotic gene expression. Characterization results confirmed the successful synthesis of BRU-AuNPs with an average crystal size of 85.40nm and stable surface charge. Results demonstrated that BRU-AuNPs reduced MCF-7 cell viability in a dose-dependent manner, with an IC50 value of 11.47µg/mL. Treatment with BRU-AuNPs altered the antioxidant balance, increased ROS generation, depolarized mitochondrial membranes, and induced apoptosis. Additionally, BRU-AuNPs inhibited cell migration and upregulated pro-apoptotic gene expression. The synthesized BRU-AuNPs exhibit potential as a highly effective targeted delivery system for breast cancer treatment. Their ability to directly deliver BRU to tumor cells while reducing side effects and enhancing therapeutic efficacy underscores their promise in advancing breast cancer therapy. Further studies are warranted to explore their clinical potential and optimize therapeutic outcomes.

The Role of Astragalus Polysaccharide in Breast Cancer Therapy

Nowadays, breast cancer has become one of the most common malignant tumors globally, posing a serious threat to womens health. Current treatments like chemotherapy and radiation often come with significant side effects. As a traditional Chinese medicine, Astragalus polysaccharide has gained attention for its remarkable potential in breast cancer therapy. With the incidence of breast cancer increasing over the years, how to effectively control the condition and improve the quality of patients lives has become an important topic of medical research. This paper systematically reviews the key pharmacological effects of Astragalus polysaccharide and its mechanisms of anti-cancer in breast cancer therapy. These include induction of apoptosis in breast cancer cells and inhibition of breast cancer cell proliferation, invasion, and migration. Despite its promising potential, the application of Astragalus polysaccharide is still limited. This paper also discussed these limitations of Astragalus polysaccharide in the treatment of breast cancer

PH-sensitive Silk Fibroin Nanoparticles Encapsulating Β-Hydroxyisovalerylshikonin for Targeted Pancreatic Cancer Therapy.

Pancreatic cancer is a highly malignant tumor with a poor prognosis, and current treatment methods have limited effectiveness. Therefore, developing new and more effective therapeutic strategies is crucial. This study aims to establish pH-responsive silk fibroin (SF) nanoparticles encapsulating β-hydroxyisovalerylshikonin (SF@β-HIVS) to enhance the therapeutic effects against pancreatic cancer. SF@β-HIVS nanoparticles were prepared using a self-assembly technique and characterized under different pH conditions using scanning electron microscopy (SEM) and dynamic light scattering (DLS). The effects of SF@β-HIVS on the viability, apoptosis, and migration of PANC-1 cells were assessed through in vitro experiments. Additionally, in vivo experiments using a PANC-1 xenograft mouse model evaluated the antitumor activity and biosafety of SF@β-HIVS. SF@β-HIVS nanoparticles exhibited a uniformly distributed spherical structure under pH 7.4 conditions and rapidly disintegrated in acidic environments, releasing the drug. In vitro experiments demonstrated that SF@β-HIVS significantly inhibited PANC-1 cell proliferation, induced apoptosis, and suppressed cell migration. In vivo, experiments confirmed the significant antitumor activity and good biosafety of SF@β-HIVS. This study successfully developed pH-responsive SF@β-HIVS nanoparticles and validated their potential in treating pancreatic cancer. These findings provided a foundation for the clinical application of SF@β-HIVS in pancreatic cancer treatment.

In Vitro Investigation of the Anti-Hepatocellular Carcinoma Activity of Peptides Derived From Quinoa (Chenopodium quinoa Willd) Bran.

Hepatocellular carcinoma (HCC) is the most common and highly aggressive tumor in the world. Although immunotherapy, surgical resection, targeted therapy and HCC transplantation could improve the prognosis for HCC patients, the tumor recurrence rate of the tumor remains high due to its insidious and invasive nature. Therefore, the development of new HCC therapeutic agents has become particularly important. Quinoa is abundant in bioactive peptides, proteins, and other functional ingredients that confer various health benefits to humans. Quinoa bran, the outer seed coat of quinoa, like quinoa, has extremely high nutritional value and rich protein content. This study firstly found that hydrolysate from quinoa bran protein (QBPP) exhibited targeting anti-HCC effect on the proliferation of HepG2 and Bel-7402 HCC cells in a concentration dependent manner, without significant toxic side effects on normal human liver cells L02. Further, QBPP exerted anti-HCC effect through mitochondria-mediated apoptosis and inhibition of HCC cells migration. Collectively, QBPP shows potential as a next-generation dietary supplement for the prevention and treatment of HCC.

Anticancer, Apoptotic, Cell Migration and Invasion Inhibition and in silico Molecular Docking Studies of Naringetol in A-549 Human Lung Cancer Cells

Anticancer, Apoptotic, Cell Migration and Invasion Inhibition and in silico Molecular Docking Studies of Naringetol in A-549 Human Lung Cancer Cells

Anionic polymer coating for enhanced delivery of Cas9 mRNA and sgRNA nanoplexes.

Polymeric carriers have long been recognized as some of the most effective and promising systems for nucleic acid delivery. In this study, we utilized an anionic di-block co-polymer, PEG-PLE, to enhance the performance of lipid-modified PEI (C14-PEI) nanoplexes for delivering Cas9 mRNA and sgRNA targeting KRAS G12S mutations in lung cancer cells. Our results demonstrated that PEG-PLE, when combined with C14-PEI at a weight-to-weight ratio of 0.2, produced nanoplexes with a size of approximately 140 nm, a polydispersity index (PDI) of 0.08, and a zeta potential of around -1 mV. The PEG-PLE/C14-PEI nanoplexes at this ratio were observed to be both non-cytotoxic and effective in encapsulating Cas9 mRNA and sgRNA. Confocal microscopy imaging revealed efficient endosomal escape and intracellular distribution of the RNAs. Uptake pathway inhibition studies indicated that the internalization of PEG-PLE/C14-PEI primarily involves scavenger receptors and clathrin-mediated endocytosis. Compared to C14-PEI formulations, PEG-PLE/C14-PEI demonstrated a significant increase in luciferase mRNA expression and gene editing efficiency, as confirmed by T7EI and ddPCR, in A549 cells. Sanger sequencing identified insertions and/or deletions around the PAM sequence, with a total of 69% indels observed. Post-transfection, the KRAS-ERK pathway was downregulated, resulting in significant increases in cell apoptosis and inhibition of cell migration. Taken together, this study reveals a new and promising formulation for CRISPR delivery as potential lung cancer treatment.