期刊
FRONTIERS IN CHEMISTRY
卷 7, 期 -, 页码 -出版社
FRONTIERS MEDIA SA
DOI: 10.3389/fchem.2019.00366
关键词
MARK4; paclitaxel; Hepatocellular carcinoma; drug resistance; inhibitor
资金
- National Natural Science Foundation of China [81772960, 81572739, 81702980, 21861142007]
- Key Research and Development Project of Sichuan Province [19ZDYF2612]
- Sichuan Science and Technology Program [2019JDTD0013]
- Fundamental Research Funds for the Central Universities [2018SCUH0088]
- Postdoctoral Science Foundation of Sichuan University [2019SCU12037]
- 1.3.5 Project for Disciplines of Excellence, West China Hospital, Sichuan University [ZYJC18030]
Hepatocellular carcinoma (HCC) is one of the most prevalent cancers worldwide. Nowadays, pharmacological therapy for HCC is in urgent needs. Paclitaxel is an effective drug against diverse solid tumors, but commonly resisted in HCC patients. We recently have disclosed that microtubule affinity-regulating kinase 4 (MARK4) increases the microtubule dynamics and confers paclitaxel resistance in HCC, suggesting MARK4 as an attractive target to overcome paclitaxel resistance. Herein, we synthesized and identified coumarin derivatives 50 as a novel MARK4 inhibitor. Biological evaluation indicated compound 50 directly interacted with MARK4 and inhibited its activity in vitro, suppressed cell viability and induced apoptosis of HCC cells in a MARK4-dependent manner. Importantly, compound 50 significantly increased the drug response of paclitaxel treatment to HCC cells, providing a promise strategy to HCC treatment and broadening the application of paclitaxel in cancer therapy.
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