目的探讨β-榄香烯对多药耐药胃癌细胞SGC7901/Adr的耐药逆转及其对聚腺苷二磷酸聚合酶(PARP)和β-糖蛋白(P-gp)表达的影响。方法采用MTF法检测细胞的药物敏感性及耐药逆转,流式细胞术检测细胞内药物累积,流式细胞术PI染色检测细胞凋亡,Western blot检测蛋白表达。结果β-榄香烯对胃癌SGC7901及SGC7901/Adr细胞均具有增殖抑制作用,且具有量效关系。阿霉素与低毒剂量β-榄香烯共同作用SGC7901/Adr细胞,其IC50显著降低(P〈0.05),耐药逆转倍数为1.41.与阿霉素单药组相比,加入低毒剂量β-榄香烯后,细胞内阿霉素的蓄积浓度明显增加,差异有统计学意义(P〈0.05)。β-榄香烯作用后诱导PARP裂解,同时下调了β-即蛋白表达。结论β-榄香烯部分逆转SGC7901/Adr细胞对阿霉素的耐药性,其机制与增加细胞内阿霉素的蓄积,诱导PARP裂解及降低P—gP的表达有关。
Objective To explore the effect of β-elemene on the reverse of multi-drug resistance and the expressions of the poly ADP-ribose polymerase protein (PARP) and P-glyeopmtein (P-gp) in SGC7901/Adr cells. Methods MTT method was used to detect the sensitivity of cell and its reverse of multi-drug resistance. Intracellular accumulation of adriamycin in SGC7901/Adr cells was observed by fluorescent-spectropbotometry. Cell apoptosis was determined by flow cytometry after propidium iodide staining. Expressions of proteins were detected by Western blot. All experimental data were dealt with by SPSS ( 13.0 soft). Results The inhibitory effect of [3-elemene on both SGC7901 and SGC7901/Adr was detected in a dose-dependent manner. Low-cytotoxic dose of β-elemene could obviously decrease the IC50 value of SGC7901/Adr cells to adriamycin (P 〈 0.05 ). The reversing fold was 1.41. Low-cytotoxic dose of β-elemene could increase the intracellular accumulation of adriamycin evidently and remarkably induce the activated fragment of PARP and decrease the P-gp expression in SGC7901/ Adr cells. Conclusion [3-elemene could partially reverse the multi-drug resistance to adriamycin in SGC7901/Adr cells,which is related to the increased accumulation of intraeellular adriamycin, the activated fragment of PARP and the decreased expression of P-gp.