Tumor Chemosensitivity is Correlated with Expression of Multidrug Resistance Associated Factors in Variously Differentiated Gastric Carcinoma Tissues

Li, Yong; Tan, Bi-Bo; Zhao, Qun; Liu, Fan; Liu, Yü; Hao, Yingjie; Zhao, Xue-Feng

doi:10.5754/hge12535

Cited by 7 publications

(7 citation statements)

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“…[24][25][26][27] The two main mechanisms are as follows: first, the classic resistance mechanism, that is, energy-dependent 'drug pump' mechanism mediated by membrane glycoprotein, and resistance proteins in this category include P-gp, MDR-related protein, LRP and so on; the second category is the resistance mechanism mediated by the enzyme, including resistant proteins Topo, GST-π, thymidylate synthase and protein kinase C. 28 Studies also found that many genes that affected tumor cell apoptosis, including Bcl-2 and Bax were also closely associated with MDR of tumors. [29][30][31] However, research on Vav3 and drug resistance of gastric cancer has not been reported.…”

Section: Discussionmentioning

confidence: 99%

Inhibition of Vav3 could reverse the drug resistance of gastric cancer cells by downregulating JNK signaling pathway

Tan

Zhao

et al. 2014

Cancer Gene Ther

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This study aims to investigate the effect and mechanism of Vav3 on the multidrug resistance of gastric cancer. Fluorescence quantitative RT-PCR and western blot assay were used to detect Vav3 and drug resistance genes in gastric cancer tissues as well as gastric cell lines such as SGC7901, SGC7901/adriamycin (ADR) and GES-1. Besides, Vav3-specific small interfering RNA (Vav3-siRNA) was applied to inhibit Vav3 in SGC7901/ADR, and SRB assay was used to determine chemosensitivity. After that, drug resistance genes and proteins in MAPK and PI3K/AKT signaling pathway were detected after Vav3-siRNA transfection. The results showed that overexpressed Vav3 was found in gastric cancer tissues and SGC7901 and SGC7901/ADR cells. Activity of SGC7901/ADR cells transfected with Vav3-siRNA combined with 5-fluorouracil/oxaliplatin was much lower than that of control groups, and MDR1/P-gp, GST-π and Bcl-2, Bax genes were significantly downregulated in Vav3-siRNA transfection group. AKT, ERK and p38 total protein and their phosphorylation levels showed no significant change in Vav3-siRNA-transfected SGC7901/ADR cells, whereas the ratio of C-Jun phosphorylation levels to total C-Jun protein was significantly downregulated. The results suggested that Vav3 may play a role in drug resistance of gastric cancer by inhibiting drug resistance genes MDR1/P-gp, GST-π and Bcl-2 through regulating the JNK signaling pathway.

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Section: Discussionmentioning

confidence: 99%

Inhibition of Vav3 could reverse the drug resistance of gastric cancer cells by downregulating JNK signaling pathway

Tan

Zhao

et al. 2014

Cancer Gene Ther

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“…Adjuvant chemotherapy after operation has been considered as necessary to eliminate systemic micrometastases and remnant malignant cells to the fullest extent possible, ultimately improving survival [ 11 , 12 ]. Unfortunately, so far, this kind of adjuvant treatment strategy has been disappointing as a result of multidrug resistance (MDR) of malignant cells to different chemotherapeutic agents [ 13 , 14 ]. Therefore, detection and evaluation of MDR genes or proteins may help guide adjuvant chemotherapy in gastric cancer and determine the prognosis of patients.…”

Section: Discussionmentioning

confidence: 99%

Expression of multidrug resistance-associated proteins and their relation to postoperative individualized chemotherapy in gastric cancer

Cheng

et al. 2014

World J Surg Onc

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BackgroundAdjuvant chemotherapy could reduce residual tumor cells and prevent relapse, however, not all patients are suitable for adjuvant chemotherapy. Screening appropriate patients based on molecular markers for individualized adjuvant chemotherapy is necessary.MethodsBetween June 2002 and June 2004, 119 patients who underwent radical gastrectomy were retrospectively analyzed. Some patients had adjuvant chemotherapy based on platinum and 5-FU for four to six cycles. Topoisomerase II (ToPo II) negative, multidrug resistance protein (MRP) positive and glutathione S-transferase π (GST-π) positive were regarded as three risk factors that may be associated with chemotherapy resistance and poor prognosis. Patients were divided into two groups: a high-risk group (≥2 risk factors) and a low-risk group (<2 risk factors), and tumor recurrence and patient survival time of the two groups were analyzed.ResultsThe average recurrence time of the low-risk group was significantly longer than that of the high-risk group (21.29 ± 11.10 versus 15.16 ± 8.05 months, P <0.01). The 3-year and 5-year survival rates of the high-risk group were 57.4% and 42.6%, however, it had no significant difference compared to 66.2% and 58.5% of the low-risk group (P >0.05). In the high-risk group, the 3-year survival rates of patients with/without chemotherapy were 62.1% and 52.0% and the 5-year survival rates were 44.8% and 40.0%, respectively, but the difference was not statistically significant (P >0.05). In the low-risk group, the 3-year survival rates of patients with/without chemotherapy were 81.2% and 51.5%, and the 5-year survival rates were 71.9% and 45.5%, respectively, these differences were statistically significant (P <0.05).ConclusionsCombined detection of the multidrug resistance (MDR)-related proteins ToPo II, MRP and GST-π may be prospectively valuable for postoperative individualized chemotherapy and in further predicting the outcomes of gastric cancer patients.

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“…Studies have demonstrated that the overexpression of BCL-2 is associated with chemoresistance to cytotoxic chemotherapeutic agents in patients with gastric cancer[ 47 , 48 ]. The silencing of BCL-2 increased cell apoptosis and decreased resistance to 5-FU in gastric adenocarcinoma cells[ 49 ].…”

Section: Dysregulation Of Cell Survival and Deathmentioning

confidence: 99%

Molecular mechanisms of chemoresistance in gastric cancer

Shi

Gao

2016

WJGO

129

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Gastric cancer is the fourth most common cancer and the second leading cause of cancer deaths worldwide. Chemotherapy is one of the major treatments for gastric cancer, but drug resistance limits the effectiveness of chemotherapy, which results in treatment failure. Resistance to chemotherapy can be present intrinsically before the administration of chemotherapy or it can develop during chemotherapy. The mechanisms of chemotherapy resistance in gastric cancer are complex and multifactorial. A variety of factors have been demonstrated to be involved in chemoresistance, including the reduced intracellular concentrations of drugs, alterations in drug targets, the dysregulation of cell survival and death signaling pathways, and interactions between cancer cells and the tumor microenvironment. This review focuses on the molecular mechanisms of chemoresistance in gastric cancer and on recent studies that have sought to overcome the underlying mechanisms of chemoresistance.

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Tumor Chemosensitivity is Correlated with Expression of Multidrug Resistance Associated Factors in Variously Differentiated Gastric Carcinoma Tissues

Abstract: Different MDR characteristics were exhibited in well and poorly differentiated gastric carcinomas, which may be caused by different expressed MDR associated factors in these tissues.

Cited by 7 publications

References 0 publications

Inhibition of Vav3 could reverse the drug resistance of gastric cancer cells by downregulating JNK signaling pathway

Inhibition of Vav3 could reverse the drug resistance of gastric cancer cells by downregulating JNK signaling pathway

Expression of multidrug resistance-associated proteins and their relation to postoperative individualized chemotherapy in gastric cancer

Molecular mechanisms of chemoresistance in gastric cancer

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