Pirarubicin inhibits multidrug-resistant osteosarcoma cell proliferation through induction of G2/M phase cell cycle arrest.

Acta Pharmacologica Sinica
Shui-er ZhengYang Yao

Abstract

Pirarubicin (THP) is recently found to be effective in treating patients with advanced, relapsed or recurrent high-grade osteosarcoma. In this study, the effects of THP on the multidrug-resistant (MDR) osteosarcoma cells were assessed, and the underlying mechanisms for the disruption of cell cycle kinetics by THP were explored. Human osteosarcoma cell line MG63 and human MDR osteosarcoma cell line MG63/DOX were tested. The cytotoxicity of drugs was examined using a cell proliferation assay with the Cell Counting Kit-8 (CCK-8). The distribution of cells across the cell cycle was determined with flow cytometry. The expression of cell cycle-regulated genes cyclin B1 and Cdc2 (CDK1), and the phosphorylated Cdc2 and Cdc25C was examined using Western blot analyses. MG63/DOX cells were highly resistant to doxorubicin (ADM) and gemcitabine (GEM), but were sensitive or lowly resistant to THP, methotrexate (MTX) and cisplatin (DDP). Treatment of MG63/DOX cells with THP (200-1000 ng/mL) inhibited the cell proliferation in time- and concentration-dependent manners. THP (50-500 ng/mL) induced MG63/DOX cell cycle arrest at the G(2)/M phase in time- and concentration-dependent manners. Furthermore, the treatment of MG63/DOX cells with THP (20...Continue Reading

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Citations

Dec 17, 2015·Cancer Metastasis Reviews·Yunfei LiaoZhenfeng Duan
Sep 5, 2015·Journal of Orthopaedic Surgery and Research·Xiao-Rong YangRen-Rong Gong
Aug 28, 2019·International Journal of Hyperthermia : the Official Journal of European Society for Hyperthermic Oncology, North American Hyperthermia Group·Jun ZhouTao Du
Apr 23, 2019·Experimental and Therapeutic Medicine·Xiaoou ZhouJianjun Xiong
May 14, 2021·Phytomedicine : International Journal of Phytotherapy and Phytopharmacology·Xue YangXianBo Wang
Jan 6, 2018·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Lei XueJinhua Luo

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