bcl-2家族BH3-only蛋白在依托泊苷诱导胃腺癌细胞凋亡中的作用

Association of BH3 only Proteins with Etoposide-Induced Apoptosis of Gastric Adenocarcinoma Cells

目的研究bcl-2家族BH3-only蛋白Noxa、Bim和PUMA在依托泊苷诱导胃腺癌细胞凋亡中的作用。方法Annexin V-FITC染色,流式细胞仪(FCM)检测细胞凋亡率,半定量RT-PCR检测细胞中BH3-only蛋白的mRNA表达量。结果依托泊苷诱导胃腺癌细胞凋亡具有剂量、时间依赖性,SGC-7901细胞系比BGC-823更加敏感,100μM的依托泊苷作用48小时后SGC-7901的凋亡率达到50%,而BGC-823的凋亡率只有20%。BH3-only蛋白Noxa的mRNA表达明显上调,Bim少量上调与依托泊苷诱导的细胞凋亡有关系;相反,PUMA的mRNA表达量在依托泊苷治疗前后没有变化。结论依托泊苷诱导的胃腺癌细胞凋亡与BH3-only蛋白Noxa和Bim表达上调有关联。

Objective To study the potential role of BH3-only proteins of the bcl-2 family in Etoposide-induced apoptosis of gastric adenocarcinoma cells. Methods FITC-conjugated Annexin V staining was used to detected apoptotic cells in flow cytometry. The expression levels of mRNA for BH3-only proteins were measured by semi-quantitative RT-PCR. Results Etoposide induced apoptosis of gastric adenocarcinoma cells in a dose- and time-dependent manner. It appeared that SGC-7901 cells are more sensitive to the compound than BGC-823 cells. While about 50% of SGC-7901 cells were found to be apoptotic, only 20% of BGC-823 cells appeared to be killed after treatment with etoposide at 100μM for 48 hours. Induction of apoptosis by Etoposide was associated with up-regulation of mRNAs for the BH3 only proteins Noxa, and to a lesser extent, Birn. In contrast, the expression levels of mRNAs for PUMA remained unchanged before and after treatment with Etoposide. Conclusion Induction of apoptosis of gastric adenocarcinoma calls by Etoposide may be assocaited with up-regulation of the BH3 only proteins of the bcl-2 family, Noxa and Birn.