蝎毒对人乳腺癌MCF-7/ADM细胞多药耐药的影响及机制研究

Effect of BMK on multidrug resistance reversal and glutathione s-transferase activity in human breast cancer MCF-7/ADM cell line

关键词:  蝎毒  逆转  谷胱甘肽S转移酶  MCF-7/ADM细胞株

Key words:  BMK  reverse  glutathione s-transferase  MCF-7/ADM cell line

摘要:

［目的］探讨蝎毒(BMK)对人乳腺癌MCF-7/ADM细胞多药耐药的逆转及谷胱甘肽S转移酶（GST）活性的影响。［方法］实验分两组：MCF-7/ADM耐药细胞组；MCF-7/ADM＋蝎毒组。采用MTT法测定蝎毒的细胞毒性和抗药性逆转，流式细胞术测定蝎毒对耐药细胞凋亡百分率的影响，紫外分光光度术测定蝎毒对谷胱甘肽S-转移酶（GSTs）活性的影响。［结果］与MCF-7/ADM耐药细胞组相比：①非细胞毒性剂量（3.0μg/mL）蝎毒能显著降低MCF-7/ADM的IC50（P<0.01），逆转倍数为1.52倍。②蝎毒(3.0 μg/mL)显著增强对耐药细胞的凋亡诱导作用，凋亡率由（8.9±0.01）%上升为（12.6±0.21）%（P<0.01）。③蝎毒(3.0 μg/mL)显著降低耐药细胞内谷胱甘肽S转移酶的活性（P<0.01）。［结论］蝎毒能够部分逆转人乳腺癌MCF-7/ADM细胞对阿霉素的耐药性，增加ADM对肿瘤细胞的凋亡诱导作用，其逆转机制与降低耐药细胞内GST酶活性有关。

Abstract:

［Objective］To study the effect of inducing apoptosis and resistance reversing on BMK combined with ADM in human breast cancer MCF-7/ADM cell line. ［Methods］ The major groups were divided as follows:MCF-7/ADM cell lines；MCF-7/ADM cell lines with BMK.The cytotoxicity and the reversal of resistance of BMK were assessed by MTT assay. The apoptosis percentage were determined by the flow cytometry. The glutathione s-transferase activity were determined by the UV-spectrophotometry.［Results］Compared with MCF-7/ADM cell lines：①The non-cytotoxic dose of BMK(3　μg/mL) significantly decreased the IC50 value of ADM（P<0.01）.Its reversal folds is 1.52.②BMK(3 μg/mL) increased the apoptosis inducing effect of ADM to MCF-7/ADM cells, which of apoptosis percentage was increased from （8.9±0.01）% to （12.6±0.21）%（P<0.01）. ③BMK (3μg/mL) could significantly decrease glutathione s-transferase activity in MCF-7/ADM cells（P<0.01）.［Conclusion］ BMK could partially reverse resistance to ADM and increase the apoptosis in human breast cancer MCF-7/ADM cell line，which is related to decreasing glutathione s-transferase activity.