JAK2/STAT3信号通路对A549细胞株中HIF-1ɑ、VEGF蛋白表达的影响

目的：研究人肺腺癌细胞A549细胞中JAK2/STAT3信号通路对HIF-1ɑ、VEGF蛋白表达的影响。方法：AG490处理在氧含量正常及缺氧条件下（CoCl2200μmol/L）48h后Westernblot法测定A549细胞中HIF-1ɑ、VEGF蛋白表达变化（分组为对照组、AG49050μmol/L、AG490100μmol/L、CoCl2、CoCl2＋AG49050μmol/L和CoCl2＋AG490100μmol/L组）。IL-6（3.85nmol/L）处理A549细胞24h后,检测细胞中STAT3、p-STAT3、HIF-1ɑ、VEGF蛋白表达变化（分组为对照组,IL-6组）。结果：JAK2特异性抑制剂AG490作用48h后,相对于对照组AG490能够下调HIF-1ɑ、VEGF的蛋白表达,且呈浓度依赖性;随浓度的升高,抑制作用更明显。缺氧条件下（CoCl2200μmol/L）能够上调HIF-1ɑ、VEGF的蛋白表达。AG490也能够下调CoCl2诱导的HIF-1ɑ、VEGF的蛋白表达,且呈浓度依赖性,随浓度的升高,抑制作用更显著。IL-6能够上调HIF-1ɑ、VEGF的蛋白表达。结论：在人肺腺癌细胞A549细胞中,缺氧可上调HIF-1α和VEGF蛋白表达。JAK2/STAT3信号通路对HIF-1α和VEGF蛋白的表达具有调节作用。

Effects of JAK2/STAT3 on the expression of HIF -1α ,VEGF in A549 lung cancer cell line

Objective： To observe the effects of JAK2 /STAT3 on the protein expression of HIF-1ɑ and VEGF in human lung adenocarcinoma A549 cell line. Methods： The JAK inhibitor AG490,Co Cl2 and interleukin-6（ IL-6）were added to the culture media of A549 cell line. The expression levels of HIF-1ɑ and VEGF in human lung adenocarcinoma A549 cell line after treated with AG490 and Co Cl2 for 48 hours were detected by Western blot（ control,AG490 50μmol / L,AG490 100μmol / L,Co Cl2,Co Cl2＋ AG490 50μmol / L,Co Cl2＋ AG490 100μmol / L）. Western blot was used to examine the protein expression levels of STAT3,p-STAT3,HIF-1ɑ,VEGF in A549 cell line after treatment with IL-6（ 3. 85 nmol / L） for 24 hours（ control,IL-6）. Results： After treated with AG490 for 48 hours,the protein levels of HIF-1α and VEGF were reduced in a concentration-dependent manner. In other words,the levels of HIF-1α and VEGF were decreased more obvious with higher AG490 concentration. IL-6 can increase the protein expression of HIF-1ɑ,VEGF. Conclusion： Hypoxia could increase the expression of HIF-1α and VEGF in human lung adenocarcinoma A549 cell line. Besides,the JAK2 / STAT3 signaling pathway could regulate the expression of HIF-1α and VEGF.