Vol 42(2008) N 1 p. 91-97;
X. Li, R. Fan, X. Zou, L. Hong, L. Gao, H. Jin, R. Du, L. He, L. Xia, D. Fan
Reversal of multidrug resistance of gastric cancer cells by downregulation of CIAPIN1 with CIAPIN1 siRNAState Key Laboratory of Cancer Biology and Institute of Digestive Diseases, Xijing Hospital, the Fourth Military Medical University, 17 Changle Western Road, Xi'an, 710032, China
Received - 2007-02-19; Accepted - 2007-04-18
The overexpression of a new cytokine-induced apoptosis inhibitor 1 (CIAPIN1) gene has been shown previously to promote a multidrug resistant phenotype in gastric cancer cells through the upregulation of MDR1 and MRP1. In the present study, we constructed the siRNA eukaryotic expression vectors of CIAPIN1 and transfected them into SGC7901/VCR cells to examine whether the downregulation of CIAPIN1 increased cell sensitivity towards chemotherapeutic drugs. After transfection, the expression of CIAPIN1 was dramatically decreased in CIAPIN1 siRNA transfectants compared with that in parental cells and empty vector control cells. The downregulation of CIAPIN1 significantly enhanced the sensitivity of SGC7901/VCR cells to vincristine (VCR), adriamycin (ADR), and etoposide (VP-16), but not to 5-fluorouracil (5-Fu) and cisplatin (CDDP). Cell capacity to efflux adriamycin decreased markedly in CIAPIN1 siRNA transfectants, and the correlation between CIAPIN1 downregulation and decreased MDR-1 transcriptional activity was observed. CIAPIN1 siRNA could significantly downregulate the expression of Bcl-2, and upregulate the expression of Bax, but does not alter the expression of PTEN in gastric cancer cells. These observations suggested that the siRNA constructs of CIAPIN1 we obtained could effectively downregulate the expression of CIAPIN1 and reverse the resistant phenotype of gastric cancer cells. Further study of the biological functions of CIAPIN1 may be helpful for understanding the mechanisms of multidrug resistance of gastric cancer and in developing possible strategies to treat gastric cancer.
CIAPIN1, multidrug resistance, apoptosis, gastric cancer, RNAi