转染缺氧诱导因子-1α对肺癌细胞A549生长的影响

目的:研究缺氧诱导因子-1α(HIF-1α)对人肺癌细胞株A549体内、外生长的影响,并探讨其可能机制。方法:将HIF-1α转染人肺癌细胞A549中,观察A549细胞生长。建立人肺癌裸鼠模型,随机将其分为两组:对照组(A组,10只),HIF-1α转染细胞组(B组,10只)。1月后,切除瘤灶、称瘤重、计算促瘤率。标本用免疫组化测定增殖细胞核抗原(PCNA),同时用Westernblot检测HIF-1α、凋亡抑制蛋白survivin和bcl-2的表达。结果:HIF-1α转染A549细胞后,细胞生长速率加快。转染HIF-1α的裸鼠肿瘤生长较对照组快,A组、B组的瘤重分别为(2.51±0.33)g,(3.44±0.40)g,促瘤率为37%。免疫组化和Westernblot提示:B组的PCNA表达比A组高,B组HIF-1α、survivin、bcl-2的蛋白水平明显高于A组。结论:转染HIF-1α体内、外均可促进肺癌A549细胞的生长,其机制可能与其能促进细胞恶性增殖和抑制凋亡有关。

Influence of hypoxia-inducible factor-1 alpha on lung cancer cell A549 growth in vitro and in vivo

AIM: To study the role of hypoxia-inducible factor-1alpha(HIF-1α) on lung cancer cells A549 growth in vitro and in vivo. METHODS: To observe the growth rate of A549 cells after HIF-1α transfected, A549 cells (1×10⁶/mouse) were inoculated subcutaneously into 20 nude mice, which were randomly divided into two groups: the control group (group A, n=10), the HIF-1α transfected group(group B, n=10). The weights of subcutaneous tumor were detected. The resected specimens were made into paraffin-embedded sections. The proliferating cell nuclear antigen (PCNA) was identified by immunohistochemistry(ISH). The expressions of HIF-1α、 apoptosis-related protein survivin and bcl-2 were analyzed by Western blot. RESULTS: The growth rates of the HIF-1α transfected lung cancer cells A549 were significantly increased, and more importantly, the HIF-1α transfected lung cancer cells A549 was able to enhance lung cancer growth in nude mice(P＜0.05). The PCNA were increased significantly in group B, compared with group A. The expressions of HIF-1α, survivin and bcl-2 in group B were increased significantly than that of group A. CONCLUSIONS: HIF-1α increases lung cancer cells A549 growth in vitro and in vivo and its mechanism may be due to promotion of proliferation and inhibition of apoptosis.