Wu Huita, Deng Jie, Yu Shiying, Wang Xin, Chen Yuan
Department of Oncology, Zhongshan Hospital, Xiamen University, Xiamen, 361004, China.
J Huazhong Univ Sci Technolog Med Sci. 2010 Feb;30(1):108-12. doi: 10.1007/s11596-010-0120-6. Epub 2010 Feb 14.
In order to investigate the inhibitory effects of Endostar (rh-endostatin, YH-16) in combination with radiotherapy on lung adenocarcinoma A549 in mice and the interaction mechanisms of combined therapy, the transplantation tumor models of A549 lung adenocarcinoma were established. When the largest diameter of tumor reached 1.0 cm, all nude mice were randomly divided into 4 groups: Endostar group, radiotherapy group, radiotherapy plus Endostar (combined treatment) group, and control group (n=6 in each group). The largest diameter and the vertical diameter of tumor were measured at different time points. At the 16th day, mice were executed, and the tumors were applied to analysis of rate of tumor cell apoptosis, and the expression levels of basic fibroblast growth factor (bFGF) mRNA were detected by reverse transcription-polymerase chain reaction (RT-PCR) and those of vascular endothelial growth factor (VEGF) by immunohistochemistry. The results demonstrated that the rate of tumor inhibition in combined treatment group was higher than that in other groups. And the rate of tumor cell apoptosis in combined treatment group was also higher than that in other groups. Meanwhile, the levels of bFGF mRNA and VEGF expression in combined treatment group were lower than those in other groups. It was concluded that Endostar obviously enhanced the curative effectiveness of radiotherapy on lung adenocarcinoma A549 in mice. The underlying mechanisms may involve the down-regulation of bFGF mRNA and VEGF expression to inhibit angiogenesis by Endostar and the cooperative effect of Endostar and radiotherapy to synergistically promote tumor cell apoptosis. And Endostar inhibits angiogenesis by down-regulating the expression of bFGF mRNA and VEGF.
为研究恩度（重组人血管内皮抑制素，YH-16）联合放疗对小鼠肺腺癌A549的抑制作用及联合治疗的相互作用机制，建立了A549肺腺癌移植瘤模型。当肿瘤最大直径达到1.0 cm时，将所有裸鼠随机分为4组：恩度组、放疗组、放疗联合恩度（联合治疗）组和对照组（每组n = 6）。在不同时间点测量肿瘤的最大直径和垂直直径。第16天处死小鼠，取肿瘤进行肿瘤细胞凋亡率分析，采用逆转录-聚合酶链反应（RT-PCR）检测碱性成纤维细胞生长因子（bFGF）mRNA表达水平，免疫组织化学法检测血管内皮生长因子（VEGF）表达水平。结果显示，联合治疗组的肿瘤抑制率高于其他组。联合治疗组的肿瘤细胞凋亡率也高于其他组。同时，联合治疗组的bFGF mRNA水平和VEGF表达低于其他组。结论：恩度明显增强了放疗对小鼠肺腺癌A549的治疗效果。其潜在机制可能包括恩度下调bFGF mRNA和VEGF表达以抑制血管生成，以及恩度与放疗协同促进肿瘤细胞凋亡。且恩度通过下调bFGF mRNA和VEGF的表达抑制血管生成。
