川芎嗪逆转肿瘤多药耐药性及其机制的研究

Reversal of multidrug resistance and its mechanism by tetramethylpyrazine

目的:探讨川芎嗪(tetrameth-ylpyrazine,TMP)逆转人乳腺癌MCF-7/ADM细胞对多柔比星(adriamycin,ADM)的耐药及其P-糖蛋白(P-glycopro-tein,P-gp)表达的影响。方法:MTT法测定细胞的药敏性,荧光分光光度法检测细胞内多柔比星浓度的变化,流式细胞术检测耐药细胞凋亡率的变化,流式细胞术观测细胞P-gp的表达。结果:非细胞毒性剂量(320mg/L)川芎嗪能显著降低MCF-7/ADM的IC50(P=0·0031),逆转倍数为2·13倍;且能明显增加耐药细胞ADM的浓度(P=0·0042)和凋亡率(P=0·0026);320mg/L川芎嗪使耐药细胞的P-gp表达率由(90·6±0·41)%降低至(69·1±1·65)%。结论:川芎嗪具有部分逆转人乳腺癌MCF-7/ADM细胞对多柔比星的耐药性,其逆转机制可能与抑制该细胞P-gp的表达有关。

OBJECTIVE： To explore the effect of tetramethylpyrazine （TMP）on reversal of multidrug resistance to adriamycin （ADM） and the expression of P-glycoprotein （P-gp） in human breast cancer MCF-7/ADM cell line. METHODS： The drug sensitivity of MCF-7/ADM cells was studied by MTT assay. The intracellular accumulation of ADM was measured by fluorescent-spectrophotometry. Cell apoptosis percentage of MCF-7/ADM was detected by flow cytometry. The expression of P-gp was determined by flow cytometry. RESULTS： The IC50 value of ADM to MCF-7/ADM cells was significantly decreased by the non-cytotoxic dose of TMP （320 mg/L）（P = 0.003 1）, which reversed the resistance by 2.13 folds. The intracellular ADM accumulation and cell apoptosis percentage in MCF-7/ADM were significantly elevated by TMP （320 mg/L）, P=0.004 2, P=0.002 6. The expression of P-gp was reduced from （90.60±0.41）% to （69.10±1.65）% by TMP in MCF-7/ADM cells. CONCLUSION： TMP could partially reverse the resistance to ADM in human breast cancer MCF-7/ADM cell line. Its reversal mechanism was related to inhibiting P-gp expression in MCF-7/ADM cells.