期刊
ONCOLOGY REPORTS
卷 36, 期 2, 页码 1180-1186出版社
SPANDIDOS PUBL LTD
DOI: 10.3892/or.2016.4892
关键词
cucurbitacin B; breast cancer; CIP2A; PP2A; multi drug dresistance; apoptosis
类别
资金
- National Natural Sciences Foundation of China [81400157]
- Natural Science Foundation of Hubei Provincial Department of Education [Q20152106]
- Hubei University of Medicine [2014QDJZR08, 2015QDJZR16]
- Foundation for Innovative Research Team of Hubei University of Medicine [2014CXX05]
- Hubei University of Medicine
- National Training Program of Innovation and Entrepreneurship for Undergraduates [201610929001]
Cancerous inhibitor of protein phosphatase 2A (CIP2A) is a human oncoprotein that is overexpressed in various tumors. A previous study found that CIP2A expression is associated with doxorubicin (Dox) resistance. In the present study, we investigated whether cucurbitacin B (CuB), a natural anticancer compound found in Cucurbitaceae, reversed multidrug resistance (MDR) and downregulated CIP2A expression in MCF-7/Adriamycin (MCF-7/Adr) cells, a human breast multidrug-resistant cancer cell line. CuB treatment significantly suppressed MCF-7/Adr cell proliferation, and reversed Dox resistance. CuB treatment also induced caspase-dependent apoptosis, decreased phosphorylation of Akt (pAkt). The suppression of pAkt was mediated through CuB-induced activation of protein phosphatase 2A (PP2A). Furthermore, CuB activated PP2A through the suppression of CIP2A. Silencing CIP2A enhanced CuB-induced growth inhibition, apoptosis and MDR inhibition in MCF-7/Adr cells. In conclusion, we found that enhancement of PP2A activity by inhibition of CIP2A promotes the reversal of MDR induced by CuB.
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