Down regulation of CIAPIN1 reverses multidrug resistance in human breast cancer cells by inhibiting MDR1.
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.
Department of Oncology, the Second Affiliated Hospital of Harbin Medical University, Harbin 150086, China. ludan1972@medmail.com.cn
Dan
D
Lu
Zhibo
Z
Xiao
Wenxiu
W
Wang
Yuqing
Y
Xu
Shujian
S
Gao
Lili
L
Deng
Wen
W
He
Yu
Y
Yang
Xiaofei
X
Guo
Xuemei
X
Wang
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000235:genetics; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism*; D002453:Cell Cycle / Q000187:drug effects / Q000235:genetics; D045744:Cell Line, Tumor; D015536:Down-Regulation / Q000187:drug effects / Q000235:genetics; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D020128:Inhibitory Concentration 50; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000970:Antineoplastic Agents; C489114:CIAPIN1 protein, human; D047908:Intracellular Signaling Peptides and Proteins; D034741:RNA, Small Interfering; D016159:Tumor Suppressor Protein p53