Icariin enhances cytotoxicity of doxorubicin in human multidrug-resistant osteosarcoma cells by inhibition of ABCB1 and down-regulation of the PI3K/Akt pathway

Biological & Pharmaceutical Bulletin
Zhendong WangLingyi Kong

Abstract

Multidrug resistance is one of the major causes limiting the efficacy of chemotherapeutic agents used to control osteosarcoma. Multidrug resistance protein 1 (MDR1 or ABCB1) was considered to play a critical role in multidrug resistance. Agents from traditional Chinese medicines (TCMs) have great potential to prevent the onset or delay the progression of the carcinogenic process, and also to enhance the efficacy of mainstream antitumor agents. Herein, we investigated the effect and mechanism of icariin in the human osteosarcoma doxorubicin (DOX)-resistant cell line MG-63/DOX. In this study, icariin exhibited significant effects in sensitization of the resistant cancer cells at a concentration non-toxic to doxorubicin. It also increased the intracellular doxorubicin accumulation and retention in MG-63/DOX cells. In addition, an increase in Rh123 accumulation and a decrease in Rh123 efflux were observed in MG-63/DOX cells treated with icariin, indicating a blockage of the activity of MDR1. Furthermore, icariin enhanced the apoptosis induced by doxorubicin and down-regulated the expression of MDR1. The mechanism involves the inhibition of phosphatidyl inositol 3-kinase (PI3K)/Akt signaling. In conclusion, icariin possesses a rever...Continue Reading

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Citations

Jul 23, 2016·Frontiers in Pharmacology·Hui-Li TanBey-Hing Goh
Jun 18, 2017·Tumour Biology : the Journal of the International Society for Oncodevelopmental Biology and Medicine·Yuanyuan TangYun Liu
Dec 21, 2017·Evidence-based Complementary and Alternative Medicine : ECAM·Xiangyu DengZengwu Shao
Jan 5, 2019·Journal of Cellular and Molecular Medicine·Yantao ChenQing He
May 26, 2017·Evidence-based Complementary and Alternative Medicine : ECAM·Xiangyu DengHongzhi Hu
Aug 9, 2018·Brazilian Journal of Medical and Biological Research = Revista Brasileira De Pesquisas Médicas E Biológicas·Meili TianXinpeng Yan
Jun 30, 2019·Critical Reviews in Microbiology·Rene Christena LowrenceSaisubramanian Nagarajan

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