线粒体靶向药物联合氯喹克服肿瘤多药耐药研究

Study on Mitochondrial Targeted Drugs Combined with Chloroquine to Overcome Multidrug Resistance in Cancer

目的研究线粒体靶向药物三苯基膦修饰的多柔比星(triphenylphosphine-doxorobicin,TPP-DOX)联合自噬抑制剂氯喹逆转慢性白血病耐药细胞K562/ADR的耐药作用。方法制备线粒体靶向药物TPP-DOX;采用CCK8法检测TPP-DOX、DOX及二者联合氯喹引起的K562/DOX细胞毒性情况;流式分析TPP-DOX、DOX及二者联合氯喹入胞情况及周期抑制情况;比色法分析凋亡因子caspase-3和caspase-9的表达。结果TPP-DOX联合氯喹可明显逆转K562/DOX耐药情况,提高caspase-3和caspase-9的表达。TPP-DOX并不能引起细胞周期阻滞,说明TPP-DOX并未通过入核发挥作用。结论TPP-DOX联合氯喹可有效克服K562/DOX细胞耐药情况。

OBJECTIVE To study the reversal effect of mitochondrial targeting drug triphenylphosphine-doxorobicin(TPP-DOX)combined with autophagy inhibitor chloroquine on drug resistance of K562/ADR cells in chronic leukemia.METHODS Mitochondrion targeting drug TPP-DOX was prepared.Then CCK8 method was used to measure cell cytotoxicity of K562/DOX after the treatment of TPP-DOX,DOX and their chloroquine combinations.Cell uptake and cell cycle arrest of TPP-DOX,DOX and their chloroquine combination were measured through flow cytometer.The expression of caspase-3 and caspase-9 were examined by using a colorimetric method.RESULTS TPP-DOX combined with chloroquine significantly reversed the drug resistance of K562/DOX cell,and increased the expression of caspase-3 and caspase-9.TPP-DOX couldn’t cause cell cycle arrest,indicating that TPP-DOX did not play a role through nuclear entry.CONCLUSION TPP-DOX and chloroquine successfully overcame the drug resistance of K562/DOX.