Apoptosis Of Gastric Carcinoma Cells Research Articles

Retracted] MicroRNA‑133a inhibits proliferation and invasion, and induces apoptosis in gastric carcinoma cells via targeting fascin actin‑bundling protein1.

Following the publication of this paper, it was drawn to the Editors' attention by a concerned reader that certain of the flow cytometric data in the article (featured in Fig. 4B) were strikingly similar to data that had appeared in different form in another article by different authors. Owing to the fact that the contentious data in the above article had already appeared in different form in another article prior to its submission to Molecular Medicine Reports, the Editor has decided that this paper should be retracted from the Journal. After having been in contact with the authors, they agreed with the decision to retract the paper. The Editor apologizes to the readership for any inconvenience caused. [the original article was published on Molecular Medicine Reports 34: 1473‑1478, 2015; DOI: 10.3892/mmr.2015.3545].

Circular RNA PLEC acts as a sponge of microRNA-198 to promote gastric carcinoma cell resistance to paclitaxel and tumorigenesis

Gastric carcinoma (GC) is one of the most frequent types of malignancy worldwide. Resistance to paclitaxel (PTX) has become an obstacle to the prognosis of GC, and the underlying mechanism is not clear. A previous study identified GC-related circRNAs via microarray analysis and bioinformatics analysis, and we discovered that circPLEC (hsa_circ_104722) was markedly upregulated in GC tissues and cells. The molecular mechanism of circPLEC in PTX-resistant GC cells still needs to be explored. In the present study, qRT-PCR demonstrated that circPLEC was upregulated in PTX-resistant GC tissues and cells, indicating that circPLEC boosts the PTX resistance of GC. circPLEC downregulation weakened GC resistance to PTX and tumorigenesis, migration and invasion and promoted the apoptosis of PTX-resistant GC cells. MiR-198 inhibitor reversed the effect of circPLEC downreguAlation in PTX-resistant GC cells, and MUC19 downregulation weakened GC resistance to PTX and tumorigenesis and improved the apoptosis of PTX-resistant GC cells. In summary, circPLEC acts as a sponge of miR-198 to promote the PTX resistance and tumorigenesis of GC cells by regulating MUC19 expression.

Downregulation of SDCBP inhibits cell proliferation and induces apoptosis by regulating PI3K/AKT/mTOR pathway in gastric carcinoma.

Syndecan-binding protein (SDCBP) has been reported to critically process a core role in tumorigenesis. This study was conducted to characterize a novel regulatory network of SDCBP in gastric carcinoma (GC) cells. Our findings indicated that overexpression of SDCBP promoted the proliferation of GC cell and increased proliferating cell nuclear antigen (PCNA) expression. Moreover, the overexpression of SDCBP suppressed the apoptosis of GC cell along with a decrease of Bax/Bcl-2 ratio and induction of PI3K/AKT/mTOR activation. However, knockdown of SDCBP exhibited opposed effects on GC cells. Furthermore, silencing SDCBP significantly inhibited GC cell viability and PCNA expression accompanied with the upregulated cell apoptosis and Bax/Bcl-2 ratio, which was regulated by PI3K/AKT/mTOR signaling pathway. And it was further determined that PI3K inhibitor LY294002, AKT inhibitor Torin1, and mTOR inhibitor MK-2206 suppressed the apoptosis. In conclusion, SDCBP promotes the growth ability of GC by inducing the PCNA expression and inhibiting GC cell apoptosis via inactivation of the PI3K/AKT/mTOR pathway.

Translational control of Bcl-2 promotes apoptosis of gastric carcinoma cells

BackgroundAnti-apoptotic protein Bcl-2 plays a substantial role in the carcinogenesis, whereas the regulation for Bcl-2 in gastric carcinoma (GC) is poorly understood. Specifically, a role of microRNA (miR)-383 in the control of Bcl-2 has not been shown in GC and thus addressed in the current study.MethodsWe investigated the levels of miR-383 and Bcl-2 in 50 GC specimens, and compared them with patients’ clinical characteristics. Bioinformatics analyses and luciferase-reporter assay were applied for analyzing the relationship between Bcl-2 and miR-383. An CCK assay was used to determine the survival of Fluorouracil-treated GC cells, and apoptosis of GC cells was assessed by flow cytometric FITC Annexin V apoptosis detection assay and expression of apoptosis-associated proteins.ResultsThe levels of miR-383 were lower while the levels of Bcl-2 levels were higher in GC specimens, compared to tissue from the adjacent non-tumor region. Low miR-383 and high Bcl-2 seemed to be associated with high malignancy and metastasis. In GC specimens, the levels of Bcl-2 and miR-383 inversely correlated. The overall survival of miR-383-low cases was poorer. Mechanistically, miR-383 targeted the 3′-UTR of Bcl-2 mRNA to inhibit its protein translation. Overexpression of miR-383 downregulated Bcl-2, resulting in reduced survival of Fluorouracil-treated GC cells. Similar conclusion was drawn through analysis of published database.ConclusionMiR-383 reduces survival of Fluorouracil-treated GC cells through downregulating of Bcl-2.

LncRNA HEIH promotes cell proliferation, migration and invasion by suppressing miR-214-3p in gastric carcinoma.

The present study aimed to investigate the function of long non-coding RNA HEIH in gastric carcinoma (GC). Adjacent normal tissues and GC tissues were obtained from 72 patients. Real-time quantitative polymerase chain reaction (RT-qPCR) was utilized to measure the expression of HEIH in cancer tissues and cells. Cell Counting Kit-8 and transwell assays were employed to evaluate cell proliferation, migration and invasion. An Annexin V-fluorescein-isothiocyanate (FITC)/propidium iodide (PI) Apoptosis Detection Kit was used to evaluate the apoptosis ratio. RT-qPCR was used to detect the expression level of miR-214-3p. The expression of HEIH in GC tissues was higher than in adjacent normal tissues. The expression of HEIH was upregulated in MKN-45, NCL-N87, KATO III cell lines compared within normal gastric epithelial cells. Knockdown of lncRNA HEIH significantly decreased the number of migrated and invaded cells. Additionally, downregulation of HEIH could increase GC cell apoptosis compared with the non-specific control (NC) group. We also proved that miR-214-3p was the direct target of lncRNA HEIH, and that overexpression of miR-214-3p could reverse the effects of HEIH. Silencing of HEIH could suppress Gastric Carcinoma cell proliferation, migration and invasion by inhibiting miR-214-3p. Thus, HEIH might represent a novel biomarker and therapeutic target.

Circular RNA Paired-Related Homeobox 1 Promotes Gastric Carcinoma Cell Progression via Regulating MicroRNA-665/YWHAZ Axis.

Gastric carcinoma (GC) is a ubiquitous malignant tumor worldwide. Circular RNA paired-related homeobox 1 (circ-PRRX1), one kind of non-coding RNAs, has been reported to act as a promoter in tumor growth. This study aims to explore the effects of circ-PRRX1 on proliferation, apoptosis, and metastasis in GC and the underlying regulatory mechanisms. The expression of circ-PRRX1, miR-665, and tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein zeta (YWHAZ) mRNA was analyzed by quantitative real-time polymerase chain reaction (qRT-PCR). Western blot was used to analyze YWHAZ protein expression.3-(4, 5-dimethyl-2-thiazolyl)-2, 5-diphenyl-2-Htetrazolium bromide (MTT), flow cytometry, and transwell assay were carried out to assess the viability, apoptosis, migration, and invasion in GC cells. The interaction between miR-665 and circ-PRRX1 or YWHAZ was predicted by StarBase v2.0 and identified by dual-luciferase reporter system. Xenograft mouse model was employed to determine the effects of circ-PRRX1 knockdown on GC growth in vivo. Compared with normal tissues and cells, circ-PRRX1 and YWHAZ levels were upregulated, and miR-665 was downregulated in GC tissues and cells. Functionally, circ-PRRX1 knockdown inhibited the viability, migration, and invasion and promoted apoptosis in GC cells, whereas anti-miR-665 abolished these effects. Mechanistically, circ-PRRX1 was confirmed as a sponge of miR-665 to regulate YWHAZ expression. Xenograft mouse model suggested that circ-PRRX1 knockdown reduced GC cells growth in vivo. Circ-PRRX1 knockdown suppressed GC development by targeting miR-665 to inhibit YWHAZ expression, and the potential molecular mechanism may provide a theoretical basis for GC therapy.

Upregulation of microRNA-650 by PBX1 is correlated with the development of Helicobacter pylori-associated gastric carcinoma.

Helicobacter pylori (HP) infection induces the development of gastric carcinoma (GC), one of the most frequent and fatal cancers worldwide, via a progressive cascade. The roles of microRNAs (miRNAs) involved in the cascade and the behind mechanisms, however, are still unclear. This study was designed to investigate the expression of miR-650, a well-recognized oncogenic miRNA in GC samples and to analyze the associations between this miRNA and HP infection, and the molecular mechanism. Following miRNA- and mRNA-based microarray analyses, miR-650, pre-B-cell leukemia transcription factor 1 (PBX1), and LATS2 were filtered as targets. After that, function assays were implemented to assess their function in GC cells. miR-650 was upregulated in HP+ tissues and cells, and inhibition of miR-650 attenuated cell proliferation, invasion, migration, yet enhanced apoptosis. PBX1 was overexpressed in HP+ tissues and cells and promoted miR-650 transcription. Overexpression of PBX1 abrogated the effect of the miR-650 inhibitor on GC cells. miR-650 targeted LATS2, and LATS2 was poorly expressed in HP+ tissues and cell lines. Simultaneous knockdown of miR-650 and LATS2 reduced GC cell apoptosis. These results display that upregulation of miR-650 induced by HP infection and PBX1 dampens LATS2 in GC cells, potentially offering novel intervention targets for GC.

N6-(2-hydroxyethyl)-Adenosine Induces Apoptosis via ER Stress and Autophagy of Gastric Carcinoma Cells In Vitro and In Vivo.

Gastric cancer is the most common malignant tumor of the digestive tract and is great challenge in clinical treatment. N6-(2-Hydroxyethyl)-adenosine (HEA), widely present in various fungi, is a natural adenosine derivative with many biological and pharmacological activities. Here, we assessed the antineoplastic effect of HEA on gastric carcinoma. HEA exerted cytotoxic effects against gastric carcinoma cells (SGC-7901 and AGS) in a dose and time-dependent manner. Additionally, we found that HEA induced reactive oxygen species production and mitochondrial membrane potential depolarization. Moreover, it could trigger caspase-dependent apoptosis, promoting intracellular Ca2+-related endoplasmic reticulum (ER) stress and autophagy. On the other hand, HEA could significantly inhibit the growth of transplanted tumors in nude mice and induce apoptosis of tumor tissues cells in vivo. In conclusion, HEA induced apoptosis of gastric carcinoma cells in vitro and in vivo, demonstrating that HEA is a potential chemotherapeutic agent for gastric carcinoma.

Effect of verapamil in the reversal of doxorubicin chemotherapy resistance in advanced gastric cancer.

Gastric carcinoma is one of the most common malignant tumors and one of the most common cancer-related fatal diseases. Chemotherapy is considered as the major therapy for advanced gastric cancer, and the curative effect of chemotherapy directly affects the treatment of advanced gastric cancer. Drug resistance of tumor cells is one of the important causes that induces failure of chemotherapy. Previous studies have demonstrated that verapamil (VER) can reverse drug resistance by inhibiting the P-glycoprotein (P-gp), which is one of the main targets of VER. The present study aimed at investigating the function of glucosylceramide synthase (GCS) in the VER-induced reversal of doxorubicin (ADM) chemotherapy resistance in gastric carcinoma. In the current study, the 4 GC cell line was selected for investigation. The IC50 values of gastric cancer cells were measured using CCK-8 assay. The expression levels of candidate genes in gastric carcinoma cells were measured by RT-qPCR. The expression levels of candidate protein in gastric carcinoma cells were measured by Western blot. The expression of GCS protein in clinical specimens of GC receiving VER+TACE therapy was measured by immunohistochemistry. The test of gastric carcinoma cell apoptosis was measured by Annexin V-FITC/PI double-staining. We found that the expression levels changes of the GCS gene can influence the effects of ADM+VER on cell apoptosis. The role and mechanism of GCS gene in reversing the chemotherapy resistance of gastric carcinoma cells to ADM were explored. In future research, we will explore the mechanism of how GCS affects drug resistance in gastric carcinoma and related signal transduction pathway.

Circular RNA PTK2 Accelerates Cell Proliferation and Inhibits Cell Apoptosis in Gastric Carcinoma via miR-139-3p.

Gastric carcinoma (GC) is one of the most common malignant tumors. Although increasing studies have indicated that circular RNAs function as ideal biomarkers for multiple cancers, only a few researches elucidated the correlation between circular RNA PTK2 (circPTK2) and human cancers. To further explore the expression status, biological function, and regulatory mechanism of circPTK2 in GC. Bioinformatics analysis and function or mechanism experiments including RT-qPCR, flow cytometry, Western blot, luciferase reporter assay, and xenografts assays were applied to investigate the function of circPTK2 and miR-139-3p. High expression of circPTK2 was presented in GC tissues and cells. The circPTK2 knockdown notably suppressed cell proliferation and promoted cell apoptosis in GC. In mechanism, circPTK2 served as a sponge of miR-139-3p. Inhibition of miR-139-3p could reverse circPTK2 silence-mediated effects on GC cell proliferation and apoptosis. Furthermore, the xenograft tumor model was established to investigate the role of circPTK2 in GC tumor growth. Experimental results delineated that the reduction in tumor growth in response to circPTK2 knockdown was partly recovered by miR-139-3p inhibitor. CircPTK2 promotes GC development by sponging miR-139-3p, which may function as an effective gene target for managing GC.

LncRNA HOTTIP promotes proliferation and inhibits apoptosis of gastric carcinoma cells via adsorbing miR-615-3p.

To explore the role of long-noncoding ribonucleic acid HOXA transcript at the distal tip (lncRNA HOTTIP) in the proliferation and apoptosis of gastric carcinoma cells. The expressions of lncRNA HOTTIP in gastric carcinoma cell lines MGC-803, HGC-27, SNU-1, and SGC-7901 and normal gastric mucosa cell line RGM-1 were detected by real-time fluorescence quantitative polymerase chain reaction (PCR) and compared. The effects of lncRNA HOTTIP on proliferation and apoptosis of gastric carcinoma cells were detected by cell counting kit-8 (CCK-8), colony formation assay, and flow cytometry, respectively. StarBase v2.0 website was adopted to predict the relationship between lncRNA HOTTIP and target miRNAs. Dual-Luciferase reporter assay was performed to verify the sponge effect of lncRNA HOTTIP on miR-615-3p. CCK-8 experiment was conducted to detect its effect on proliferation of gastric carcinoma cells after co-silencing lncRNA HOTTIP and miR-615-3p. LncRNA HOTTIP was highly expressed in gastric carcinoma cell lines MGC-803, HGC-27, SNU-1, and SGC-7901 than in normal gastric mucosa cell line RGM-1. After knockdown of lncRNA HOTTIP, the proliferation function of gastric carcinoma cells was markedly weakened, and the proportion of apoptotic cells increased. LncRNA HOTTIP was able to adsorb miR-615-3p via a sponge effect. Notably, knockdown of miR-615-3p restored the effect of silenced lncRNA HOTTIP on the proliferation function of gastric carcinoma cells. LncRNA HOTTIP is highly expressed in gastric carcinoma cells. It affects cell proliferation and apoptosis in gastric carcinoma by adsorbing miR-615-3p via a sponge effect.

Targeted Regulation of FoxO3a by miR-372 to Mediate Gastric Carcinoma Cell Apoptosis and DDP Drug Resistance.

Background: FoxO3a is a well-studied tumor suppressor gene in the forkhead transcriptional factor O (FoxO) subfamily and its downregulation is correlated with the occurrence of gastric cancer (GC). GC tissues had microRNA (miR)-372 upregulation, which has targeted relationship with 3'-untranslated region (3'-UTR) of FoxO3a gene. This study investigated if miR-372 plays a role in modulating FoxO3a expression, and affecting GC cell proliferation, apoptosis, and cisplatin (DDP) resistance. Materials and Methods: Dual luciferase reporter gene assay assessed the targeted regulation between miR-372 and FoxO3a. DDP-resistant cell lines MGC803/DDP and MKN28/DDP were compared for gene expression against parental cells. Cell proliferation was measured by Cell Counting Kit-8 (CCK-8) assay. Cultured cells were transfected with miR-372 mimic or miR-negative control (NC) to measure FoxO3a mRNA and protein expression. Cell apoptosis and proliferation were tested by flow cytometry and 5-Ethynyl-2'-deoxyuridine (EdU) staining, respectively. Results: miR-372 had a targeted relationship with FoxO3a mRNA. MGC803/DDP and MKN28/DDP cells had significantly elevated miR-372 level than parental cells, while Foxo3a mRNA or protein levels were significantly decreased. CCK-8 assay revealed significantly lower inhibitory activity on cell proliferation in drug-resistant cells. Compared with miR-NC group, miR-273 inhibitor transfected DDP-resistant cells had significantly increased Foxo3a expression, enhanced cell apoptosis, reduced proliferation, and drug resistance. Conclusions: miR-372 upregulation is associated with DPP resistance of GC cells. Downregulation of miR-372 can inhibit proliferation, facilitate apoptosis, and suppress DDP resistance of drug-resistant GC cells.

Garcinol acts as an antineoplastic agent in human gastric cancer by inhibiting the PI3K/AKT signaling pathway.

Gastric cancer (GC) is one of the most common malignancies worldwide; however, treatment options other than surgery remain limited. Neoadjuvant chemotherapy has the potential to suppress of gastric tumorigenesis. Garcinol has been reported to exert inhibitory effects on the progression of numerous carcinomas. However, its effects in GC remain unclear. Therefore, the aim of the present study was to investigate the effects of garcinol on the proliferation, invasion and apoptosis of gastric carcinoma cells and then to explore the underlying mechanisms. Garcinol significantly decreased the proliferation and invasion of GC cells and increased apoptosis in a dose-dependent manner. Additionally, the expression of AKTp-Thr308, cyclin D1, Bcl-2, BAX, matrix metalloprotease (MMP-2) and MMP-9 in HGC-27 cells following treatment with garcinol. The results obtained in the present study suggested that garcinol may inhibit gastric tumorigenesis by suppressing the PI3K/AKT signaling pathway.

Active Monomer RTR-1 Derived from the Root of Rhodomyrtus t omentosa Induces Apoptosis in Gastric Carcinoma Cells by Inducing ER Stress and Inhibiting the STAT3 Signaling Pathway.

PurposeRhodomyrtus tomentosa, a flowering plant from the Myrtaceae family, is considered an antitumour substance with versatile biological and pharmacological activities. RTR-1 is an active monomer purified from the root of Rhodomyrtus tomentosa. However, the detail of mechanism involving in RTR-1 anti-cancer activity remains to be elucidated, and the effect on gastric cancer cells is unknown.MethodsCell proliferation was determined by MTT and clone formation assay. The effect of RTR-1 on cell cycle distribution and apoptosis was analysed utilizing flow cytometry, respectively. Moreover, Western blotting was used to detect the expression of cell cycle- and apoptosis-related protein.ResultsBased on MTT and clone formation assay, we noticed that RTR-1 inhibited the proliferation of gastric carcinoma (BGC823 and SGC7901) cells in a dose- and time-dependent manner. Furthermore, the results of flow cytometry and Western blotting showed that RTR-1 induced cell cycle arrest in the G2/M phase through the ATM-Chk2-p53-p21 signaling pathway and induced cell apoptosis by inhibiting the signal transducers and activators of transcription 3 (STAT3) pathway and activating the endoplasmic reticulum stress (ER stress) pathway.ConclusionTaken together, these results demonstrate that RTR-1 induces cell cycle arrest and promotes apoptosis in gastric carcinoma, indicating its potential application for gastric cancer therapy.

Role of Long Non-Coding RNA Zinc Finger E-Box Binding Homeobox 1 Antisense 1 in Regulating the microRNAs-200b/Wnt1 Axis Effects on Proliferation, Invasion, and Apoptosis of Gastric Carcinoma Cells

ZEB1-AS1 is an Long non-coding RNA (lncRNA) that is abnormally expressed in various tumor types and affects tumor etiology and progression. ZEB1-AS1 can affect the malignant progression of gastric cancer through the miRNA-200b/Wnt1 axis. However, its effect on proliferation, invasion, and apoptosis of gastric cancer is unclear. Using BGC-803 cells, we studied the effects of lncRNA ZEB1-AS1 and miRNA-200b on the proliferation, invasion, and apoptosis of gastric cancer. Using qRT-PCR, we found that the expression of ZEB1-AS1 was significantly increased and the expression of miRNA-200b was significantly decreased in BGC-803 cells. By CCK-8, Transwell, and flow cytometry assays, we also found that down-regulation of ZEB1-AS1 and upregulation of miRNA-200b inhibited the proliferation and invasion of BGC-803 cells and promoted apoptosis. Furthermore, upregulation of ZEB1-AS1 and miRNA-200b reversed these effects. LncRNA ZEB1-AS1 inhibits the proliferation and invasion of gastric cancer cells and induces apoptosis by regulating the miRNA-200b/Wnt1 molecular axis.

MiR-361-5p exerts tumor-suppressing functions in gastric carcinoma by targeting syndecan-binding protein.

MiR-361-5p, a tumor-related microRNA, has been reported to be implicated in the tumorigenesis and progression of diverse types of human malignancies; however, its role in gastric carcinoma remains unclear. This study aimed to explore the biological role of miR-361-5p in gastric carcinoma and clarify the potential mechanisms involved. In the present study, miR-361-5p was found to be significantly downregulated in both gastric carcinoma tissues and cell lines. Functional studies demonstrated that enhanced expression of miR-361-5p suppressed gastric carcinoma cell proliferation in vitro, inhibited tumor growth in vivo, and induced gastric carcinoma cell apoptosis. Moreover, the tumor-suppressing effects of miR-361-5p in gastric carcinoma were abrogated by the miR-361-5p inhibitor treatment. Notably, syndecan-binding protein was downregulated by miR-361-5p via direct binding to its 3' untranslated region in gastric carcinoma cells. Furthermore, syndecan-binding protein expression was discovered to be markedly upregulated and inversely correlated with miR-361-5p expression in gastric carcinoma tissues. Mechanistic studies revealed that restoring the expression of syndecan-binding protein alleviated miR-361-5p-induced inhibitory effects on proliferation of gastric carcinoma cells. Taken together, these findings suggest that miR-361-5p functions as a tumor suppressor in gastric carcinoma by directly targeting syndecan-binding protein and that miR-361-5p might be a novel therapeutic target for gastric carcinoma.

Epstein-Barr virus miR-BART1-3p suppresses apoptosis and promotes migration of gastric carcinoma cells by targeting DAB2.

Although Epstein-Barr virus (EBV) is known to encode over 40 different miRNAs of its own, the roles of most EBV miRNAs remain unknown. Disabled homolog 2 (DAB2) is a putative tumor suppressor, but its role in gastric carcinoma (GC), especially in EBV-associated GC, needs to be clarified. Our qRT-PCR and mRNA microarray results showed that DAB2 expression was down-regulated in EBV-positive GC cells compared to EBV-negative cells. Four BART miRNAs that might target DAB2 were predicted, and we found, using a luciferase reporter assay, that miR-BART1-3p directly targeted the 3'-UTR of DAB2. The miR-BART1-3p transfection decreased DAB2 expression at both mRNA and protein levels, while transfection of an inhibitor of miR-BART1-3p, miR-BART1-3p(i), increased DAB2 expression. In addition, miR-BART1-3p as well as siDAB2 increased migration and decreased apoptosis. Meanwhile, miR-BART1-3p(i) or pcDNA3.1-DAB2 transfection decreased migration and increased apoptosis in EBV-infected GC cells. Furthermore, decreased migration by miR-BART1-3p(i) was abrogated by co-transfected siDAB2, while decreased migration by miR-BART1-3p(i) was further suppressed by a co-transfected DAB2 over-expression vector. Our data suggest that miR-BART1-3p plays an important role in the tumorigenesis of EBV-associated GC by directly targeting DAB2.

Overexpression of the zinc-α2-glycoprotein accelerates apoptosis and inhibits growth via the mTOR/PTEN signaling pathway in gastric carcinoma cells

Adipocytokine alpha-2-glycoprotein 1 (AZGP1) is a 41-kDa protein which regulates insulin sensitivity and glycolipid metabolism. Recently, mounting evidence has indicated that AZGP1 plays a vital role in the progression and prognosis of many types of tumors, including hepatocellular carcinoma. Also, previous research has reported that AZGP1 levels are reduced significantly in patients with gastric carcinoma (GC). Here, we aim to assess the potential role and molecular mechanism underlying AZGP1-mediated regulation of GC progression. Both RT-PCR and Western blot methods demonstrated that AZGP1 levels were decreased in all GC cell lines tested, which included AGS, NCI-N87, MKN-28, SGC-7901 and MKN-45, relative to the normal human gastric mucosa epithelial (GES-1) cell line. Cell survival and proliferation rates were correspondingly were reduced, while cell apoptosis and caspase-3 activity were increased in NCI-N87 and SGC-7901 cells with high levels of AZGP1. Additionally, the mTOR signaling pathway was suppressed, whereas PTEN expression was elevated following transfection of NCI-N87 and SGC-7901 cells with an AZGP1 overexpressing plasmid. PTEN inhibition reversed the effects of AZGP1 on cell growth and apoptosis in SGC-7901 cells. Therefore, we conclude that AZGP1 induced apoptosis and growth inhibition in GC cells via the regulation of the mTOR/PTEN signaling pathway.

Modified Liangfu granule exhibits anti-cancer effects in gastric cancer by regulating apoptosis-related proteins and genes

Abstract Objective To investigate the anti-cancer effects and mechanism of modified Liangfu granule (MLFG) in BGC-823 gastric cancer cells. Methods The drug serum was extracted from abdominal aorta of Wistar rats treated by cyclophosphamide, dioscin, MLFG (high-, medium-, and low-dose), respectively. MTS assay was performed to detect the effect of different concentrations of MLFG and dioscin on cell growth. The effect of MLFG on cellular apoptosis was detected by flow cytometry. Western blot was used to examine Bcl-2 and Akt in BGC-823 cells treated with MLFG. Quantitative real-time polymerase chain reaction assay was performed to determine the expression level of caspase-3, E2F1 and E2F3 genes in cells treated by MLFG- and dioscin-containing serum. Results MLFG- and dioscin-containing serum inhibited the cell proliferation of BGC-823 cells. MLFG induced gastric carcinoma cell apoptosis and inhibited the expression of Bcl-2 and Akt in a dose-dependent manner. MLFG also significantly induced the gene expression of caspase-3 and downregulated E2F1 and E2F3 gene expression. Conclusion The effect of MLFG and dioscin on inhibiting cell proliferation and induction of apoptosis of gastric cancer cells might be related to the regulation of Bcl-2 and Akt proteins and the expression of caspase-3, E2F1 and E2F3 genes.

The modification of ferroptosis and abnormal lipometabolism through overexpression and knockdown of potential prognostic biomarker perilipin2 in gastric carcinoma.

To investigate the biological relationship, mechanism between perilipin2 and the occurrence, advancement of gastric carcinoma, and explore the mechanism of lipid metabolism disorder leading to gastric neoplasm, and propose that perilipin2 is presumably considered as a potential molecular biomarker of gastric carcinoma. RNA-seq was applied to analyze perilipin2 and differentially expressed genes modulated by perilipin2 in neoplastic tissues of both perilipin2 overexpression and knockdown groups in vivo. The mechanism was discovered and confirmed by Rt-qPCR, immunoblotting, immunohistochemistry, staining and microassay, respectively. Cellular function experiments were performed by flow cytometry, CCK8, clonogenic assay, etc. RESULTS: Overexpression and knockdown of perilipin2 augmented the proliferation and apoptosis of gastric carcinoma cell lines SGC7901 and MGC803, respectively. The neoplastic cells with perilipin2-overexpression obtained more conspicuously rapid growth than knockdown group in vivo, and perilipin2 affected the proliferation and apoptosis of gastric carcinoma cells by modulating the related genes:acyl-coa synthetase long-chain family member 3, arachidonate 15-lipoxygenase, microtubule associated protein 1 light chain 3 alpha, pr/set domain 11 and importin 7 that were participated in Ferroptosis pathway. Moreover, RNA-seq indicated perilipin2 was an indispensable gene and protein in the suppression of Ferroptosis caused by abnormal lipometabolism in gastric carcinoma. Our study expounded the facilitation of perilipin2 in regulating the proliferation and apoptosis of gastric carcinoma cells by modification in Ferroptosis pathway, and we interpreted that the mechanism of gastric neoplasm caused by obesity, we also discovered that pr/set domain 11 and importin 7 are novel transcription factors relevant to gastric carcinoma. Furthermore, perilipin2probably serves not only as a diagnostic biomarker, but also a new therapeutic target.