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.

Highlights

  • Breast cancer is one of the common cancers all over the World [1]

  • We found the expression of Green Fluorescent Protein (GFP) and target gene showed no change at various clone ages, which proved the MCF7/ADM-Cytokine-induced apoptosis inhibitor 1 (CIAPIN1) RNAi cell line is of good quality (Figures 4 and 5)

  • The results indicated that the protein expression of P53 in MCF7/ADM cell lines increased after RNAi which means that CIAPIN1 may participate in multidrug resistance (MDR) of breast cancer by regulating P53 expression (Figure 10)

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Summary

Introduction

Breast cancer is one of the common cancers all over the World [1]. There are about 1,200,000 women suffering from breast cancer around the World, 500,000 of which die of this disease every year.In China, incidence of breast cancer tends to increase year by year [2]. Breast cancer is one of the common cancers all over the World [1]. There are about 1,200,000 women suffering from breast cancer around the World, 500,000 of which die of this disease every year. In China, incidence of breast cancer tends to increase year by year [2]. Breast cancer often has a poor survival rate due to late clinical presentation and rapid progression. Due to the importance of chemotherapy in treating breast cancer, the development of multidrug resistance (MDR) becomes a serious obstacle to effective chemotherapy [4]. The molecular mechanism(s) of the MDR have not yet been elucidated in breast cancer cells, some studies have reported that the mechanisms of MDR were close associated with the overexpression of P-glycoprotein (P-gp) encoded by MDR1 gene in tumor cells [5,6,7]

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