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HIF-1α siRNA leads to apoptosis of pancreatic cancer cells under hypoxic conditions
基金项目:This work was supported by a grant from Nature Science Foundation of Tianjin, China (No. 05YFSYSF01300).We thank Dr. Wenjie Wei (Pennsylvania University), Dr. Yihai Cao and Dr. Feng Wang (Karolinska Institute) for their insightful advice.
摘    要:OBJECTIVE To explore the role (HIF-1α) in the proliferation and cells under hypoxic conditions. of hypoxic inducible factor-1α apoptosis of pancreatic cancer METHODS A cassette encoding small interference RNA (siRNA) targeting HIF-1α mediated by recombinant adeno-associated virus (rAAV) was constructed, giving rAAV-siHIE rAAV-siHIF or rAAV- hrGFP was transfected into exponentially growing MiaPaCa2 cells under hypoxic conditions. Then, the expression of HIF-1α mRNA and protein, the proliferation and apoptosis of MiaPaCa2 cells were examined, using real-time PCR, Western Blot, MTT and TUNEL, respectively. RESULTS Under hypoxic conditions, rAAV-siHIF inhibited the expression of HIF-1α mRNA and protein in MiaPaCa2 cells. At the same time, rAAV-siHIF decreased MiaPaCa2 cell proliferation and induced apoptosis. However, rAAV-hrGFP had no effect on the expression of HIF-1α as well as the proliferation and apoptosis of MiaPaCa2 cells under hypoxic conditions. CONCLUSION Under hypoxic conditions, HIF-1α plays a key role in the proliferation of MiaPaCa2 cells, and inhibition of HIF- 1α expression can lead to MiaPaCa2 cell apoptosis.

关 键 词:缺氧诱导因子-1  癌细胞凋亡  胰腺癌细胞  缺氧条件  siRNA  重组腺相关病毒  实时定量PCR  细胞增殖
收稿时间:2008-03-26
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