低氧诱导因子-1对人乳腺癌细细胞系侵袭和转移能力的影响

Impact of hypoxia-inducible factor-1 on tumor invasion and metastasis in breast cancer

目的 探讨低氧诱导因子（HIF）-1对人乳腺癌细胞系侵袭和转移能力的影响.方法 对正常氧和低氧培养的细胞,采用Western blot检测细胞HIF-1α、磷酸化波形蛋白和tubulin蛋白的表达;采用小干扰RNA（siRNA）干扰MDA-MB-231和SK-BR-3细胞的HIF-1α蛋白表达;穿膜侵袭和划痕修复实验检测干扰细胞的侵袭和迁移能力.结果 多种乳腺癌细胞系均有HIF-1α蛋白的基础和低氧诱导表达,以高侵袭转移能力的细胞系MDA-MB-231表达最强;经siRNA干扰HIF-1α后, 细胞的侵袭和迁移能力随之明显减弱,磷酸化波形蛋白表达降低.结论 HlF-1促进乳腺癌细胞系的侵袭和迁移,可能成为抗肿瘤转移治疗的靶点.

Objective To investigate HIF-1 α gene expression in human breast cancer cells and the role of HIF-i in tumor metastasis and invasion. Methods Human breast cancer cell lines were cultured under normoxic or hypoxic conditions. Western blot was used to evaluate the protein expression of HIF-1α,p-vimentin and α-tubulin. Small interfering RNA targeting HIF-1α was used to block the expression of HIF1α in MDA-MB-231 and SK-BR-3 cell lines. Matrigel transwell and cell wound healing assays were used to detect the capability of cellular invasion and migration, respectively. Results Under normoxic condition,all the cell lines tested showed a base-level of HIF-1αt expression. The highest expression level of HIF-1αprotein was obtained in the MDA-MB-231 cell line, which is also noticed to be highly invasive and migratory in behavior. HIF-1α siRNA was capable of blocking the protein expression of both HIF-1α and p-vimentin and in addition, the attenuated ability of invasion and migration. Conclusion Since HIF-1 is able to promote invasion and metastasis of tumor cells, which may be considered as a target in anti-cancer therapy.