Gene’s co-expression network and experimental validation of molecular markers associated with the drug resistance of gastric cancer

2020 ◽  
Vol 14 (9) ◽  
pp. 761-773
Author(s):  
Wenqian Qi ◽  
Qian Zhang
Keyword(s):  
Gastric Cancer ◽  
Drug Resistance ◽  
Molecular Markers ◽  
Human Gastric Cancer ◽  
Cancer Resistance ◽  
Gastric Cancer Cells ◽  
Network Analyses ◽  
Potential Factors ◽  
Function Enrichment

Aim: Chemotherapy can significantly improve the overall survival rate of patients with gastric cancer; however, so far little is known about the molecular mechanism of resistance to chemotherapy. Therefore, this study was proposed to elucidate molecular markers of resistance to chemotherapeutic agent in gastric cancer. Materials & methods: Weighted gene co-expression network analyses were performed in gastric cancer cohort. The most relevant genes modules for gastric cancer resistance were selected. Gene oncology function enrichment of genes was conducted. The biological function of resistant genes were identified in vitro. Results & conclusion: Two resistant hub genes, SPTBN1 and LAMP1, were selected. Experiments showed that downregulation of SPTBN1and LAMP1 proteins significantly enhanced the sensitivity of human gastric cancer cells SGC7901 to 5-FU and cisplatin. Thus, our results provide a baseline about the potential factors of drug resistance in gastric cancer.

S100P Predicts Prognosis and Drug Resistance in Gastric Cancer

2013 ◽  
Vol 28 (4) ◽  
pp. 387-392 ◽  
Author(s):  
Fulin Ge ◽  
Changzheng Wang ◽  
Weihua Wang ◽  
Benyan Wu
Keyword(s):  
Gastric Cancer ◽  
Drug Resistance ◽  
Cancer Patients ◽  
Ectopic Expression ◽  
Human Gastric Cancer ◽  
Gastric Cancer Cells ◽  
Gastric Cancer Patients ◽  
Cancer Tissues ◽  
Normal Controls

Purpose S100P has been shown to participate in processes of various human malignancies. In this study, we analyzed the tissue expression of S100P in gastric cancer and evaluated its significance. Methods We determined the S100P expression in 156 gastric cancer patients by quantitative RT-PCR. Tumor characteristics and overall survival (OS) for each patient were examined. In vitro experiments were conducted to examine whether ectopic expression of S100P modifies the proliferation and drug resistance of gastric cancer cells. Results Higher expression of S100P occurred in human gastric cancer tissues in comparison with normal controls. Highly expressed S100P in gastric cancer was correlated with TNM stage and prognosis. The 5-year survival rate was significantly lower in patients with high levels of S100P expression than in patients with low levels of expression. Ectopic expression of S100P was associated with an increase in tumor cell proliferation and drug resistance. Conclusion The expression of S100P in human gastric cancer tissues was upregulated in comparison with normal controls. By establishing an association between S100P expression and shortened OS, increase in proliferation and drug resistance, this study indicates that S100P may be a useful prognostic marker for gastric cancer patients.

scholarly journals Oridonin induces apoptosis and reverses drug resistance in cisplatin resistant human gastric cancer cells

2017 ◽  
Vol 14 (2) ◽  
pp. 2499-2504 ◽  
Author(s):  
Zhongwei He ◽  
Xiangling Xiao ◽  
Shan Li ◽  
Yang Guo ◽  
Qiuyue Huang ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Drug Resistance ◽  
Cancer Cells ◽  
Human Gastric Cancer ◽  
Gastric Cancer Cells

Oleanolic acid induces autophagic death in human gastric cancer cells in vitro and in vivo

2016 ◽  
Vol 40 (7) ◽  
pp. 770-778 ◽  
Author(s):  
Hao Nie ◽  
Yu Wang ◽  
Yong Qin ◽  
Xing-Guo Gong
Keyword(s):  
Gastric Cancer ◽  
Cancer Cells ◽  
Oleanolic Acid ◽  
Human Gastric Cancer ◽  
Gastric Cancer Cells

Celastrol Inhibits the Proliferation and Decreases Drug Resistance of Cisplatin-Resistant Gastric Cancer SGC7901/DDP Cells

2021 ◽  
Vol 21 ◽  
Author(s):  
Dongmei Zhan ◽  
Tengyang Ni ◽  
Haibo Wang ◽  
Mengying Lv ◽  
Masataka Sunagawa ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Drug Resistance ◽  
Signaling Pathway ◽  
Resistance Index ◽  
Mtor Signaling ◽  
Control Group ◽  
Human Gastric Cancer ◽  
Cancer Resistance ◽  
Mtor Signaling Pathway ◽  
Expression Levels

Background: This study aimed to determine the effect and mechanism of Celastrol inhibiting the proliferation and decreases drug resistance of cisplatin-resistant gastric cancer cells. Objective: To explore the effect and mechanism of Celastrol on proliferation and drug resistance of human gastric cancer cisplatin-resistant cells SGC7901/DDP. Methods: The thiazole blue (MTT) method was used to detect the sensitivity of human gastric cancer cisplatin-resistant cells SGC7901/DPP to cisplatin and Celastrol to determine the Drug resistance index (DRI). According to the half inhibitory concentration (IC50) value, the action concentration of the following experimental drugs was set to reduce the cytotoxicity; Annexin V-FITC/PI double staining method was used to detect the apoptosis of SGC7901/DDP cells induced by Celastrol; Western Blot was used to examine the expression levels of P-glycoprotein (P-gp), Multidrug Resistance Associated Protein 1 (MRP1), Breast Cancer Resistance Associated Protein (Breast Cancer Resistance)-relative protein (BCRP), and mechanistic Target of Rapamycin (mTOR) pathway related proteins; Real-time fluorescence quantitative polymerase chain reaction (RT-qPCR) was used to detect the mRNA expression levels of P-gp, MRP1, and BCRP. Results: (1) Compared with the control group (We set the untreated group as the control group), the proliferation of the SGC7901/DPP cells was significantly inhibited after treating with 0.1-6.4μmol/L Celastrol in a time- and concentration-dependent manner (P<0.05). The Drug resistance index DRI of the SGC7901/DPP cells to DDP was 5.64. (2) Compared with the control group, Celastrol could significantly inhibit the proliferation and induce the apoptosis of the SGC7901/DPP cells (P<0.05). (3) The mRNA and protein expression levels of P-gp, MRP1, and BCRP in the SGC7901/DPP cells were significantly higher than those in the SGC7901 cells. However, after treating with Celastrol, the expression levels of P-gp, MRP1, and BCRP in the SGC7901/DPP cells were significantly reduced (P<0.05). (4) Compared with the control group, the Celastrol treatment also reduced the expression of the mTOR signaling pathway related proteins, suggesting that the mTOR signaling pathway may be involved in the process of Celastrol inhibiting the proliferation of the SGC7901/DDP cells and reducing their drug resistance. (5) Significantly, the combination of Celastrol and DDP reduced the expression of P-gp, MRP1, and BCRP in the SGC7901/DPP cells. Conclusion: Celastrol can inhibit the proliferation of the SGC7901/DDP cells, induce their apoptosis, and reduce the expression of drug resistance genes, probably by inhibiting the expression of the proteins related to the mTOR signaling pathway.

scholarly journals Reversal of Multidrug Resistance by the Chinese Medicine Yiqi Jianpi Huaji Decoction and the Mechanism of Action in Human Gastric Cancer SGC7901/VCR Cells

2015 ◽  
Vol 2015 ◽  
pp. 1-11 ◽  
Author(s):  
Wei-Bing Li ◽  
Yang Li ◽  
Chen Yu ◽  
Yong-Ming He
Keyword(s):  
Gastric Cancer ◽  
Mechanism Of Action ◽  
Low Dose ◽  
Chemotherapeutic Agents ◽  
Human Gastric Cancer ◽  
Gastric Cancer Cells ◽  
Future Studies ◽  
Increased Sensitivity ◽  
Induced Apoptosis

Yiqi Jianpi Huaji Decoction (YJHD), a traditional Chinese medicinal formula composed of twelve ingredients, has recently been reported to have a good clinical curative effect. The purpose of the present study was to evaluate the effects of YJHD on SGC7901/VCR gastric cancer cells and to elucidate the possible mechanism of action. First, the effects of a low dose of YJHD in combination with chemotherapeutic agents on SGC7901/VCR cells were assessed using the CCK-8 assay and flow cytometry, and the effects of YJHD on genes and proteins involved in drug resistance (MDR1, MRP, TUBB3, STMN1, and TS) were evaluated. Furthermore, transfection of SGC7901/VCR cells with siRNAs targeting these genes inhibited their expression, and the efficacy of vincristine against the cells was dramatically improved in vitro when these genes were silenced. These results demonstrate that low-dose YJHD inhibited cell proliferation, induced apoptosis, reversed MDR, and increased sensitivity to chemotherapeutic agents in vitro by downregulating P-gp, MRP, TUBB3, and STMN1 expression. MDR can be reversed by siRNAs targeting genes involved in MDR, and this strategy for cancer treatment should be evaluated in future studies.

scholarly journals Potent and specific MTH1 inhibitors targeting gastric cancer

2019 ◽  
Vol 10 (6) ◽  
Author(s):  
Wenjuan Zhou ◽  
Liying Ma ◽  
Jing Yang ◽  
Hui Qiao ◽  
Lingyu Li ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cancer Cells ◽  
Cell Lines ◽  
Malignant Tumors ◽  
Inhibitory Effect ◽  
Human Gastric Cancer ◽  
Gastric Cancer Cells ◽  
Dntp Pool ◽  
Cancer Tissues

Abstract Human mutT homolog 1(MTH1), the oxidized dNTP pool sanitizer enzyme, has been reported to be highly expressed in various malignant tumors. However, the oncogenic role of MTH1 in gastric cancer remains to be determined. In the current study, we found that MTH1 was overexpressed in human gastric cancer tissues and cells. Using an in vitro MTH1 inhibitor screening system, the compounds available in our laboratory were screened and the small molecules containing 5-cyano-6-phenylpyrimidine structure were firstly found to show potently and specifically inhibitory effect on MTH1, especially compound MI-743 with IC50 = 91.44 ± 1.45 nM. Both molecular docking and target engagement experiments proved that MI-743 can directly bind to MTH1. Moreover, MI-743 could not only inhibit cell proliferation in up to 16 cancer cell lines, especially gastric cancer cells HGC-27 and MGC-803, but also significantly induce MTH1-related 8-oxo-dG accumulation and DNA damage. Furthermore, the growth of xenograft tumours derived by injection of MGC-803 cells in nude mice was also significantly inhibited by MI-743 treatment. Importantly, MTH1 knockdown by siRNA in those two gastric cancer cells exhibited the similar findings. Our findings indicate that MTH1 is highly expressed in human gastric cancer tissues and cell lines. Small molecule MI-743 with 5-cyano-6-phenylpyrimidine structure may serve as a novel lead compound targeting the overexpressed MTH1 for gastric cancer treatment.

scholarly journals TSPAN9 suppresses the chemosensitivity of gastric cancer to 5-fluorouracil by promoting autophagy

2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Yaoyue Qi ◽  
Weiwei Qi ◽  
Shihai Liu ◽  
Libin Sun ◽  
Aiping Ding ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Drug Resistance ◽  
Cancer Cells ◽  
Transmembrane Protein ◽  
Pi3k Pathway ◽  
Drug Resistant ◽  
Gastric Cancer Cells ◽  
Autophagy Pathway ◽  
Resistant Cells

Abstract Background The issue of drug resistance in gastric cancer has attracted global attention. TSPAN9, a 4-transmembrane protein that plays an important role in tumor progression and signal transduction, has been found to be closely related to tumor invasion, metastasis, and autophagy. Methods Immunoblotting was used to evaluate TSPAN9 expression in parental and drug-resistant gastric cancer cells. Functional assays, such as the CCK-8 assay, were used to detect the proliferation of gastric cancer cells and the response of TSPAN9 to 5-fluorouracil (5-FU). Western blotting was used to analyze the expression of constituents of the PI3K/AKT/mTOR-mediated autophagy pathway induced by TSPAN9. Coimmunoprecipitation was performed to assess the specific mechanism by which TSPAN9 affects the PI3K pathway. Results We demonstrated that TSPAN9 is overexpressed in 5-FU-resistant cells compared to parental cells. 5-FU-mediated inhibition of cell proliferation can be significantly restored by increasing TSPAN9 expression, and inhibiting this expression in drug-resistant cells can restore the sensitivity of the cells to 5-FU. In addition, TSPAN9 also significantly promoted autophagy in gastric cancer cells in vitro. Further studies indicated that TSPAN9 downregulates the expression of PI3K and proteins associated with PI3K-mediated autophagy. In addition, TSPAN9 interacts with PI3K and inhibits its catalytic activity. Conclusion The current study reveals the important role of TSPAN9 in drug resistance to 5-FU in gastric cancer. It also provides a new target to clinically address drug-resistant gastric cancer and will contribute to the treatment strategy of this disease.

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