乏氧诱导因子1α在非小细胞肺癌细胞株培美曲塞化疗抵抗中的作用-肿瘤科专业论文.docxVIP

能为提高培美曲塞在人类肺癌及其他肿瘤的治疗有效率提供了新途径，若同时联 合培美曲塞应用可能提供了一种新的治疗模式。 关键词 HIF-1α 培美曲塞 肺癌 化疗抵抗 RNA 干扰 乏氧 Hypoxia induced pemetrexed resistance in human non-small cell lung cancer via hypoxia-inducible factor 1α Abstract Purpose: We have proved hypoxia conditions are connected with the occurrence and development of chemoresistance closely. Hypoxia inducible factor-1（HIF-1） is a critical transcription factor. Pemetrexed is the new chemotherapy drugs for non-small cell lung cancer treatment, but also exists chemoresistance. Our experiment study the mechanism of hypoxia induced pemetrexed resistance in human non-small cell lung cancer via hypoxia-inducible factor 1α. Methods: The A549 NSCLC cells are cultured in hypoxic conditions .the sensitivity of the cells to Pemetrexed and the cell inhibitory rate were determined by MTT assay. The expression and the transcriptional activity of HIF-1α were examined by western blot.The cell cycle distribution was analyzed by the flow cytometry. In addition, we silence HIF-1α expression via performing RNA interference. Results: (1) The MTT assay demonstrates that hypoxia substantially reduces the susceptibility of non-small cell lung cancer cells to pemetrexed. Building HIF-1α/siRNA model, knockdown of endogenous HIF-1α to prove the function of HIF-1 in hypoxia cells. Westernblot testing suggests under the hypoxia condition HIF-1α is significantly overexpressed .HIF-1α/siRNA can significantly reduce the expression of HIF-1α. The MTT assay of silencing HIF-1α by siRNA shows that the inhibiting rates of A549 cell to pemetrexed increases. There are no differences between hypoxic and normoxic conditions. Cell cycle analysis suggests that hypoxia promote G0/G1 arrest and silencing HIF-1α by siRNA switches G0/G1 arrest into the cell cycle, cell cycle arrest at the S phase increases, ultimately, recovers the responsivity of A549 cells to pemetrexed. Conclusion: Our experiment proves that hypoxia-inducible - 1 alpha via hypoxia causes non-sm