| Objective: Gastric cancer is the fifth most common malignancy in the world.Chemotherapy is still a very important therapy in the treatment of gastric cancer,but the emergence of multidrug resistance(MDR)often leads to the failure of chemotherapy.The development of MDR is usually mediated by one or more energy-dependent transporters,which detect and elute anticancer drugs from cells.These transporters include P glycoprotein P-gp/MDR1,multidrug resistance-associated protein 1(MRP1),lung cancer resistance protein(LRP),and breast cancer resistance protein(BCRP).In addition,other mechanisms have also been involved in the development of tumor acquired resistance,including insensitivity to drug-induced apoptosis.Tumor necrosis factor-related apoptosis inducing ligand(TRAIL)is one of the tumor necrosis factor(TNF)superfamily members,can selectively induce tumor cell apoptosis without damaging to normal cells.TRAIL can enhance the killing effect of chemotherapeutic drugs on tumor cells,and also has strong apoptosis effect on tumor-resistant cells and can reverse the tumor-resistant cell lines into sensitive cell lines.Studies have shown that decreasing the expression of MDR1 and MRP1 in tumor cells and upregulating the ratio of Bax / Bcl-2 can increase the sensitivity of tumor to chemotherapeutic drugs,but whether TRAIL can increase the sensitivity of the tumor to chemotherapeutic drugs through affect the expression of MDR1,MRP1 and Bax / Bcl-2 genes is unclear.In this study,we proposed to observe the different expression of MDR1,MRP1,Bcl-2,Bax gene in human gastric adenocarcinoma adriamycin-resistant cell line SGC7901 / ADR and the parental cell line SGC7901,and observed the influence of tumor necrosis factorrelated apoptosis inducing ligand(TRAIL)on multidrug resistance gene MDR1 and P-gp protein,multidrug resistant associate protein MRP1,anti-apoptotic gene Bcl-2 and pro-apoptotic gene Bax in human gastric cancer SGC7901 / ADR.Then to explore the possible genes involved in the acquired resistance of gastric cancer and the possible mechanism of TRAIL killing tumor-resistant cells and to find a new direction for gastric cancer chemotherapy.Methods:1.The drug sensitivity of SGC7901/ADR cells and their parent cells SGC7901 were detected by MTT assay.2.The m RNA expression of MDR1,MRP1,Bcl-2,Bax gene of SGC7901 / ADR and SGC7901 cells were detected by Quantitative Real-time PCR.3.SGC7901 / ADR cells were handled with different concentrations of TRAIL,Quantitative Real-time PCR and Western-blot were used to measure the expression of MDR1,MRP1,Bcl-2,Bax m RNA and protein of various genes in different treatment groups.Results: 1.MTT assay for drug sensitivity test showed that,comparing with SGC7901 cells,the IC50 of SGC7901 / ADR cells was significantly increased by vincristine and doxorubicin(all p<0.01),the IC50 of SGC7901 / ADR cells was slightly increased by cisplatin(P<0.01).2.Compared with SGC7901,the level of MDR1,MRP1,Bcl-2 m RNA expression in SGC7901 / ADR cells were significantly increased,but the level of Bax m RNA expression was decreased.3.The level of MDR1,MRP1,Bcl-2 m RNA and protein expression in SGC7901 / ADR cells were down-regulated by TRAIL,and the expression of pro-apoptotic protein Bax m RNA was up-regulated,comparing with control group,there were statistically significant differences(all P<0.05).Conclusions: TRAIL may down-regulate the expression of MDR1,MRP1,Bcl-2 and up-regulate the expression of Bax to promote the apoptosis of gastric cancer drug-resistant cells,and reverse multidrug resistance of gastric cancer drug-resistant cells. |
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