雄黄诱导MCF-7/ADM细胞凋亡及逆转其耐药性的研究

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目的探讨雄黄诱导人乳腺癌MCF-7/ADM细胞凋亡及逆转其耐药性的调节机制。方法经MTT法探讨雄黄对人乳腺癌MCF-7/ADM细胞药物敏感性的影响;用透射电镜观察凋亡细胞形态改变;应用流式细胞术,探讨凋亡抑制基因bc1-2的编码蛋白Bcl-2的改变及凋亡百分率的改变;通过荧光分光光度法观察雄黄对细胞内化疗药物阿霉素积累的影响。结果雄黄对MCF-7/ADM的耐药性有明显的逆转作用,无毒剂量(15 mg/L)及低毒剂量(25 mg/L)雄黄作用后,逆转倍数分别为2.3倍及2.8倍;出现凋亡细胞,凋亡百分率由0.6%分别增至2.0%(P<0.05)及3.4%(P<0.01);Bcl-2表达由90.2%分别降至63.6%(P<0.01)及52.7%(P<0.01);MCF-7/ADM的细胞内阿霉素浓度明显增加(P<0.01)。结论雄黄通过降低Bcl-2表达,促进细胞凋亡,增加耐药细胞内阿霉素积累量等耐药机制的调节,部分逆转了MCF-7/ADM细胞对阿霉素的耐药性。 Objective To investigate the regulatory mechanism of realgar induced apoptosis in human breast cancer MCF-7 / ADM cells and to reverse its drug resistance. Methods The effects of realgar on the drug sensitivity of human breast cancer cell line MCF-7 / ADM were investigated by MTT assay. Morphological changes of apoptotic cells were observed by transmission electron microscopy. Flow cytometry was used to detect the expression of Bc1-2, -2 changes and the percentage of apoptotic cells. Fluorescence spectrophotometry was used to observe the effect of realgar on the intracellular chemotherapeutic drug adriamycin accumulation. Results Realgar had a significant reversal effect on the drug resistance of MCF-7 / ADM cells. After the non-toxic dose (15 mg / L) and realgar (25 mg / L) (P <0.01); The percentage of apoptotic cells increased from 0.6% to 2.0% (P <0.05) and 3.4% (P <0.01) respectively; the expression of Bcl-2 decreased from 90.2% to 63.6% % (P <0.01). The concentration of doxorubicin in MCF-7 / ADM cells was significantly increased (P <0.01). Conclusion Realgar partially reverses the resistance to doxorubicin in MCF-7 / ADM cells by down-regulating the expression of Bcl-2, promoting cell apoptosis and increasing the accumulation of doxorubicin in drug-resistant cells.
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