详细记录  
题名:siRNA-mediated type 1 insulin-like growth factor receptor silencing induces chemosensitization of a human liver cancer cell line with mutant P53
作者:Jian Niu, Zonghua Xu, Xiang-nong Li and Zeguang Han
来源:Cell Biology International[IF=1.194], Volume 31, Issue 2, February 2007, Pages 156-164
URL :http://dx.doi.org/10.1016/j.cellbi.2006.09.021
日期:070415
摘要: Jian Niua, , , Zonghua Xub, Xiang-nong Lia and Zeguang Hanc

aGeneral Surgery of the First Hospital Affiliated Xuzhou Medical College, Xuzhou, China
bGeneral Surgery of the Second Hospital Affiliated Suzhou University, Suzhou, China
cChinese National Human Genome Center at Shanghai, Shanghai, China

Received 14 July 2006; revised 4 August 2006; accepted 26 September 2006. Available online 4 October 2006.

Summary

Overexpression of type 1 insulin-like growth factor receptor (IGF1R) contributes to the progression and metastasis of liver cancer, implying that IGF1R gene is a suitable target of RNA interference (RNAi) for liver cancer therapy. To investigate the possible regulation of IGF1R by P53, we examined the level of IGF1R expression in liver cancer cell lines in response to adriamycin. Levels of IGF1R mRNA and protein in cell lines with wild-type P53 decreased dramatically after P53 induction, but no such reduction of IGF1R was observed in cell lines with mutated P53. Inhibition of wild-type P53 in HEPG2 cells by small interfering RNA (siRNA) significantly upregulated the expression of IGF1R. IGF1R inhibition by siRNA in Huh7 cells with mutated P53 significantly depressed cell proliferation. To investigate the sensitivity of cancer cells to adriamycin after inhibition of IGF1R, we depressed IGF1R expression using siRNA, and then added adriamycin at an IC50 dose. After a further 48 h incubation with adriamycin, proliferation was significantly depressed in the cells treated with siRNA targeting IGF1R, in comparison with siRNA targeting scramble. Furthermore, both TUNEL and pro-caspase-3 expression assay showed a significant increase in apoptosis after combined treatment with adriamycin and siRNA targeting IGF1R. Our results demonstrate that IGF1R is downregulated by P53, and that siRNA targeting of IGF1R increases liver cancer cells sensitivity to adriamycin and promotes apoptosis. siRNA targeting of IGF1R could be potentially useful for increasing sensitivity to anti-cancer drugs, especially in drug-resistant cells with mutated P53. 38.

================  评  论  部  分=================

重要性:
分类:(参照 Faculty of 1000 的分类体系)


评语:

评论密码:   返回前页  [全部]