1. Sinomenine Sensitizes Multidrug-Resistant Colon Cancer Cells (Caco-2) to Doxorubicin by Downregulation of MDR-1 Expression.
- Author
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Liu, Zhen, Duan, Zhi-Jun, Chang, Jiu-Yang, Zhang, Zhi-feng, Chu, Rui, Li, Yu-Ling, Dai, Ke-Hang, Mo, Guang-quan, and Chang, Qing-Yong
- Subjects
COLON cancer ,CANCER cells ,DOXORUBICIN ,MULTIDRUG resistance ,GENE expression - Abstract
Chemoresistance in multidrug-resistant (MDR) cells over expressing P-glycoprotein (P-gp) encoded by the MDR1 gene, is a major obstacle to successful chemotherapy for colorectal cancer. Previous studies have indicated that sinomenine can enhance the absorption of various P-gp substrates. In the present study, we investigated the effect of sinomenine on the chemoresistance in colon cancer cells and explored the underlying mechanism. We developed multidrug-resistant Caco-2 (MDR-Caco-2) cells by exposure of Caco-2 cells to increasing concentrations of doxorubicin. We identified overexpression of COX-2 and MDR-1 genes as well as activation of the NF-κB signal pathway in MDR-Caco-2 cells. Importantly, we found that sinomenine enhances the sensitivity of MDR-Caco-2 cells towards doxorubicin by downregulating MDR-1 and COX-2 expression through inhibition of the NF-κB signaling pathway. These findings provide a new potential strategy for the reversal of P-gp-mediated anticancer drug resistance. [ABSTRACT FROM AUTHOR]
- Published
- 2014
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