Zhu Yehan, Du Xianrong, Chen Huaxin, Xie Yufeng, Sheng Weihua, Yang Jicheng
Department of Respiratory, First Affiliated Hospital in Soochow University, Suzhou 215006, China.
Sheng Wu Gong Cheng Xue Bao. 2011 Jan;27(1):85-94.
To study the chemosensitivity and the mechanisms of recombinant adenovirus vector expressing ING4 and IL-24 (Ad-ING4-IL-24) on lung adenocarcinoma in vitro and in vivo, the expression of ING4 and IL-24 in A549 cells was detected by RT-PCR and Western blotting. The growth inhibition, apoptosis rate and apoptosis body were measured by MTT, flow cytometry and Hoechst staining respectively. For in vivo study, we first established the A549 tumor model by grafting A549 cells in athymic nude mice; and then injected Ad-ING4-IL-24 into the tumors. Two weeks after injection, we killed the mice, removed the tumors, weighted and calculated the ratios of tumor-suppression. We also detected the expressions of ING4, IL-24, bax, bcl-2, VEGF with immunohistochemistry. The results indicated that ING4 and IL-24 were proved successfully transcription and expression in A549 cells. More interestingly, the joint group inhibited the growth of A549 cells and induced apoptosis. The in vivo data showed that the joint group suppressed the tumor growth conspicuously through up-regulating the expression of bax, and down-regulating the expression of bcl-2, VEGF. The study proved that Ad-ING4-IL-24 significantly enhanced the chemosensitivity to anticancer drug DDP in lung adenocarcinoma, which may related with cell apoptosis and antiangiogenesis.
为研究重组腺病毒载体表达ING4和IL-24（Ad-ING4-IL-24）对肺腺癌的体外和体内化学敏感性及机制，采用RT-PCR和蛋白质印迹法检测A549细胞中ING4和IL-24的表达。分别用MTT法、流式细胞术和Hoechst染色法检测细胞生长抑制率、凋亡率及凋亡小体。体内研究方面，首先通过将A549细胞接种于裸鼠建立A549肿瘤模型；然后将Ad-ING4-IL-24注射到肿瘤内。注射两周后，处死小鼠，取出肿瘤，称重并计算抑瘤率。还用免疫组织化学法检测ING4、IL-24、bax、bcl-2、VEGF的表达。结果表明，ING4和IL-24在A549细胞中成功转录和表达。更有趣的是，联合组抑制A549细胞生长并诱导凋亡。体内数据显示，联合组通过上调bax表达、下调bcl-2和VEGF表达显著抑制肿瘤生长。该研究证明，Ad-ING4-IL-24显著增强肺腺癌对抗癌药物顺铂的化学敏感性，这可能与细胞凋亡和抗血管生成有关。
