Hao Lin, Shi Zhen-Duo, Pang Kun, He Hou-Guang, Zhou Rong-Sheng, Pang Hui, Zhang Jun-Jie, Liu Da-Chuang, Sun Zhuo, Han Cong-Hui
Department of Urology, Xuzhou Central Hospital Xuzhou, Jiangsu, China.
Central Laboratory, Xuzhou Central Hospital Xuzhou, Jiangsu, China.
Int J Clin Exp Pathol. 2018 Oct 1;11(10):4795-4805. eCollection 2018.
Bladder cancer is one of the most common cancers. Approaches that block tumor angiogenesis are a new therapeutic strategy for locally advanced or metastatic BC. VEGF/VEGFR signaling has been obviously and negatively correlated with the progression and invasion of cancer. In this study, we constructed the recombinant adenovirus vAd-VEGFR-3 to investigate its antitumor effector . First, we used the recombinant adenovirus vAd-VEGFR-3 to infect bladder cancer cells and then collected the cell culture supernatant to treat human umbilical vein endothelial cells (HUVECs). The proliferation, migration and apoptosis of HUVECs were respectively detected by MTT, transwell and Annexin V-FITC/PI double staining. In addition, mouse bladder mucosa was injured by trypsin, and the orthotopic transplantation model of human bladder cancer was successfully constructed to clarify the anti-tumor effect of Ad-VEGFR . The results showed that Ad-VEGFR could inhibit the cancer's proliferation and migration, while promoting the apoptosis of HUVECs . Moreover, Ad-VEGFR could significantly promote the apoptosis of bladder cancer cells and then prevent tumor growth . In addition, it also down-regulated the expression levels of CD31, an endothelial cell marker which is closely related to the angiogenesis. Taken together, it suggests that the infection of adenovirus-carrying VEGFR in bladder cancer cells may inhibit blood vessel formation and prevent tumor progression.
膀胱癌是最常见的癌症之一。阻断肿瘤血管生成的方法是局部晚期或转移性膀胱癌的一种新的治疗策略。VEGF/VEGFR信号通路与癌症的进展和侵袭明显呈负相关。在本研究中，我们构建了重组腺病毒vAd-VEGFR-3以研究其抗肿瘤效应。首先，我们用重组腺病毒vAd-VEGFR-3感染膀胱癌细胞，然后收集细胞培养上清液来处理人脐静脉内皮细胞（HUVECs）。分别通过MTT、Transwell和Annexin V-FITC/PI双染法检测HUVECs的增殖、迁移和凋亡情况。此外，用胰蛋白酶损伤小鼠膀胱黏膜，成功构建了人膀胱癌原位移植模型以阐明Ad-VEGFR的抗肿瘤作用。结果表明，Ad-VEGFR可抑制癌细胞的增殖和迁移，同时促进HUVECs的凋亡。此外，Ad-VEGFR可显著促进膀胱癌细胞的凋亡，进而抑制肿瘤生长。此外，它还下调了与血管生成密切相关的内皮细胞标志物CD31的表达水平。综上所述，这表明在膀胱癌细胞中感染携带VEGFR的腺病毒可能抑制血管形成并阻止肿瘤进展。
