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Down Regulation of CIAPIN1 Reverses Multidrug Resistance in Human Breast Cancer Cells by Inhibiting MDR1
Department of Oncology, the Second Affiliated Hospital of Harbin Medical University, Harbin 150086, China
Department of Plastic Surgery, the Second Affiliated Hospital of Harbin Medical University, Harbin 150086, China
These authors contributed equally to this work.
* Author to whom correspondence should be addressed.
Received: 13 March 2012; in revised form: 11 June 2012 / Accepted: 11 June 2012 / Published: 20 June 2012
Abstract: Cytokine-induced apoptosis inhibitor 1 (CIAPIN1), initially named anamorsin, a newly indentified antiapoptotic molecule is a downstream effector of the receptor tyrosine kinase-Ras signaling pathway. Current study has revealed that CIAPIN1 may have wide and important functions, especially due to its close correlations with malignant tumors. However whether or not it is involved in the multi-drug resistance (MDR) process of breast cancer has not been elucidated. To explore the effect of CIAPIN1 on MDR, we examined the expression of P-gp and CIAPIN1 by immunohistochemistry and found there was positive correlation between them. Then we successfully interfered with RNA translation by the infection of siRNA of CIAPIN1 into MCF7/ADM breast cancer cell lines through a lentivirus, and the expression of the target gene was significantly inhibited. After RNAi the drug resistance was reduced significantly and the expression of MDR1mRNA and P-gp in MCF7/ADM cell lines showed a significant decrease. Also the expression of P53 protein increased in a statistically significant way (p ≤ 0.01) after RNAi exposure. In addition, flow cytometry analysis reveals that cell cycle and anti-apoptotic enhancing capability of cells changed after RNAi treatment. These results suggested CIAPIN1 may participate in breast cancer MDR by regulating MDR1 and P53 expression, changing cell cycle and enhancing the anti-apoptotic capability of cells.
Keywords: breast cancer; multidrug resistance; CIAPIN1gene; MDR1gene; RNA interference
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Lu, D.; Xiao, Z.; Wang, W.; Xu, Y.; Gao, S.; Deng, L.; He, W.; Yang, Y.; Guo, X.; Wang, X. Down Regulation of CIAPIN1 Reverses Multidrug Resistance in Human Breast Cancer Cells by Inhibiting MDR1. Molecules 2012, 17, 7595-7611.
Lu D, Xiao Z, Wang W, Xu Y, Gao S, Deng L, He W, Yang Y, Guo X, Wang X. Down Regulation of CIAPIN1 Reverses Multidrug Resistance in Human Breast Cancer Cells by Inhibiting MDR1. Molecules. 2012; 17(6):7595-7611.
Lu, Dan; Xiao, Zhibo; Wang, Wenxiu; Xu, Yuqing; Gao, Shujian; Deng, Lili; He, Wen; Yang, Yu; Guo, Xiaofei; Wang, Xuemei. 2012. "Down Regulation of CIAPIN1 Reverses Multidrug Resistance in Human Breast Cancer Cells by Inhibiting MDR1." Molecules 17, no. 6: 7595-7611.