Xue Tao, Feng Wenming, Yu Hongbin, Zhu Ming, Fei Maoyun, Bao Ying, Wang Xiaoyi, Ma Wenxue, Lv Guiyuan, Guan Jianming, Chen Suhong
College of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou 310053, China.
Laboratory of Molecular Medicine, First People's Hospital Affiliated to Huzhou University, Huzhou 313000, China.
Biomed Res Int. 2017;2017:6757898. doi: 10.1155/2017/6757898. Epub 2017 May 15.
Transarterial chemoembolization (TACE), a well-established treatment for unresectable hepatocellular carcinoma (HCC), blocks the arterial blood supply to the tumor, which can be short-lived as development of collateral neovessels, leading to the failure of treatment. Metastasis-associated protein 1 (MTA1) is involved in development of tumors and metastases. However, the role of MTA1 in angiogenesis is still obscure.
We detected the expression of MTA1 and hypoxia-inducible factor-1 (HIF-1) and microvessel density (MVD) value in liver tumor tissues and tumor periphery before and after TACE treatment. Hepatocellular carcinoma cell line HepG2, tube formation assay, and chorioallantoic membrane (CAM) assay were applied to explore the mechanism of MTA1 in angiogenesis.
We found that expression of MTA1 increased after TACE treatment, especially in tumor periphery, which was accompanied by markedly elevated MVD value, indicating a significant correlation between MTA1 and MVD value. Moreover, MTA1 contributed to neovascularization of residual tumors. Cellular experiments further revealed that MTA1 increased the stability and the expression of HIF-1, and overexpression of MTA1 enhanced tube formation and neovessels of chick embryos.
MTA1 is an active angiogenic regulator; our results shed light on better understanding in neovascularization, which are helpful to predict prognosis of TACE, and provide evidences for intervention to improve therapeutic effects on HCC.
经动脉化疗栓塞术(TACE)是一种成熟的不可切除肝细胞癌(HCC)治疗方法,它能阻断肿瘤的动脉血供,但由于侧支新生血管的形成,这种阻断可能是短暂的,从而导致治疗失败。转移相关蛋白1(MTA1)参与肿瘤的发生和转移。然而,MTA1在血管生成中的作用仍不清楚。
我们检测了TACE治疗前后肝肿瘤组织及肿瘤周边组织中MTA1、缺氧诱导因子-1(HIF-1)的表达及微血管密度(MVD)值。应用肝癌细胞系HepG2、管腔形成实验和鸡胚绒毛尿囊膜(CAM)实验来探讨MTA1在血管生成中的机制。
我们发现TACE治疗后MTA1表达增加,尤其是在肿瘤周边,同时MVD值显著升高,表明MTA1与MVD值之间存在显著相关性。此外,MTA1促进了残留肿瘤的新生血管形成。细胞实验进一步表明,MTA1增加了HIF-1的稳定性和表达,MTA1的过表达增强了鸡胚的管腔形成和新生血管。
MTA1是一种活跃的血管生成调节因子;我们的结果有助于更好地理解新生血管形成,有助于预测TACE的预后,并为干预措施提供依据,以提高对HCC的治疗效果。