二苯乙烯苷逆转多柔比星耐药人骨肉瘤细胞多药耐药性。
Reversal of multidrug resistance by icaritin in doxorubicin-resistant human osteosarcoma cells.
机构信息
State Key Laboratory of Natural Medicines, Department of Natural Medicinal Chemistry, China Pharmaceutical University, Nanjing 210009, China.
State Key Laboratory of Natural Medicines, Department of Natural Medicinal Chemistry, China Pharmaceutical University, Nanjing 210009, China.
出版信息
Chin J Nat Med. 2018 Jan;16(1):20-28. doi: 10.1016/S1875-5364(18)30026-8.
Multidrug resistance (MDR) is one of the major obstacles in cancer chemotherapy. Our previous study has shown that icariin could reverse MDR in MG-63 doxorubicin-resistant (MG-63/DOX) cells. It is reported that icariin is usually metabolized to icariside II and icaritin. Herein, we investigated the effects of icariin, icariside II, and icaritin (ICT) on reversing MDR in MG-63/DOX cells. Among these compounds, ICT exhibited strongest effect and showed no obvious cytotoxicity effect on both MG-63 and MG-63/DOX cells ranging from 1 to 10 μmol·L. Furthermore, ICT increased accumulation of rhodamine 123 and 6-carboxyfluorescein diacetate and enhanced DOX-induced apoptosis in MG-63/DOX cells in a dose-dependent manner. Further studies demonstrated that ICT decreased the mRNA and protein levels of multidrug resistance protein 1 (MDR1) and multidrug resistance-associated protein 1 (MRP1). We also verified that blockade of STAT3 phosphorylation was involved in the reversal effect of multidrug resistance in MG-63/DOX cells. Taken together, these results indicated that ICT may be a potential candidate in chemotherapy for osteosarcoma.
多药耐药（MDR）是癌症化疗的主要障碍之一。我们之前的研究表明，淫羊藿苷可以逆转 MG-63 多柔比星耐药（MG-63/DOX）细胞的 MDR。据报道，淫羊藿苷通常代谢为朝藿定 II 和淫羊藿次苷。在此，我们研究了淫羊藿苷、朝藿定 II 和淫羊藿次苷（ICT）对逆转 MG-63/DOX 细胞 MDR 的影响。在这些化合物中，ICT 表现出最强的作用，对 1 至 10 μmol·L 的 MG-63 和 MG-63/DOX 细胞均无明显的细胞毒性作用。此外，ICT 以剂量依赖性方式增加 rhodamine 123 和 6-羧基荧光素二乙酸酯在 MG-63/DOX 细胞中的积累，并增强 DOX 诱导的细胞凋亡。进一步的研究表明，ICT 降低了多药耐药蛋白 1（MDR1）和多药耐药相关蛋白 1（MRP1）的 mRNA 和蛋白水平。我们还验证了阻断 STAT3 磷酸化参与了 MG-63/DOX 细胞多药耐药的逆转作用。综上所述，这些结果表明 ICT 可能是骨肉瘤化疗的潜在候选药物。
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