HIF-1α在肺癌中的表达及临床意义
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常州市卫生局指导性科技计划(WZ200604)


The Expression and significance of HIF-1αin lung carcinom
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    目的:研究缺氧诱导因子-1-琢(HIF-1-琢)在低氧培养条件下肺癌细胞株及肺癌组织中的表达及临床意义-方法:采用Transwell侵袭小室测定法检测缺氧对肺癌细胞侵袭力的影响,分别采用RT-PCR法和免疫印迹(Western blot)-免疫组化法测定缺氧条件下人肺腺癌细胞株A549-小细胞肺癌细胞株H446及60例肺癌组织和20例癌旁正常肺组织中HIF-1α的 mRNA和蛋白表达-结果:两种肺癌细胞系在缺氧下侵袭力较正常时增强-随着缺氧时间的延长,肺癌细胞的HIF-1αmRNA和蛋白水平呈升高趋势(P < 0.05或P < 0.01)-肺癌组织中HIF-1α的mRNA和蛋白阳性表达率分别为90.0%-75.0%,明显高于癌旁正常肺组织的30.0%-20.0%(P < 0.01)-有淋巴结转移的表达高于无淋巴结转移者,中晚期(Ⅲ~Ⅳ期)肺癌组织中的表达高于早期(Ⅰ~Ⅱ期)(P < 0.05)-结论:氯化钴诱导缺氧上调HIF-1-琢在肺癌细胞中的表达,使之进一步耐受缺氧-HIF-1α的过表达参与了肺癌的侵袭转移,HIF-1α可成为判断肺癌生物学行为的重要指标-

    Abstract:

    Objective:To investigate the expression and clinical significance of hypoxia-inducible factor 1α(HIF-1α) in hypoxic human lung cancer cell lines and human lung carcinoma tissues. Methods:Transwell assay was used to test the invasive capacity of hypoxic lung cancer cells. The expression of HIF-1α mRNA and protein in hypoxic lung cancer cells in vitro was determined by reverse transcription-polymerase chain reaction(RT-PCR) and Western blot. The expression of HIF-1α was detected using immunohistochemistry and reverse transcription-polymerase chain reaction analyses(RT-PCR) in 60 specimens of lung carcinoma and 20 specimens of corresponding adjacent tissues. Results:The effect of hypoxia on the invasion of lung cancer cells increased. After hypoxia exposure,the HIF-1α mRNA and protein expression in lung cancer cells increased time-dependently. Compared with those in the control group,the mRNA and protein levels of HIF-1α in the hypoxic groups had more significant difference(P < 0.05 or P < 0.01). In lung carcinoma tissues,the positive expression rates of HIF-1α mRNA and proteins were 90.0% and 75.0% ,while 30.0% and 20.0% in normal lung tissues respectively,showing the expression of HIF-1α in cancer tissues were significantly different from that in normal tissues(P < 0.01). Comparing with the mRNA and protein levels of HIF-1α in lung cancer tissues of ⅠandⅡstage,there was marked increase in Ⅲ and Ⅳstage. The expression of HIF-1α in group of lymph node metastasis was higher than that in group without lymph node metastasis(P < 0.05). Conclusion:CoCl2 can up-regulate the expression of HIF-1α in lung cancer cell lines by inducing hypoxia. These hypoxia-mediated effects have the potential impact on lung cancer cells to promote its hypoxic tolerance. HIF-1-琢 overexpression plays important roles in invasion and metastasis of lung carcinoma. HIF-1-琢 may be a useful marker for evaluating the biological behaviors of lung carcinoma.

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冯春来,刘 皓,王智刚. HIF-1α在肺癌中的表达及临床意义[J].南京医科大学学报(自然科学版),2008,28(8):1031-1036

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  • 收稿日期:2008-02-20
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