Peng Xing-Chen, Wang Ming, Chen Xu-Xia, Liu Jing, Xiao Gui-Hua, Liao Hong-Li
Department of Medical Oncology, Cancer Center, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, 610041, People's Republic of China,
Mol Cell Biochem. 2014 Oct;395(1-2):265-72. doi: 10.1007/s11010-014-2135-y. Epub 2014 Jul 6.
The growth and metastasis of solid tumors depends on angiogenesis. Anti-angiogenesis therapy may represent a promising therapeutic option. Vasostatin, the N-terminal domain of calreticulin, is a very potent endogenous inhibitor of angiogenesis and tumor growth. In this study, we attempted to investigate whether plasmid-encoding vasostatin complexed with cationic liposome could suppress the growth and metastasis of hepatocellular carcinoma in vivo and discover its possible mechanism of action. Apoptosis induction of pSecTag2B-vasostatin plasmid on murine endothelial cells (MS1) was examined by flow cytometric analysis in vitro. Nude mice bearing HCCLM3 tumor received pSecTag2B-vasostatin, pSecTag2B-Null, and 0.9 % NaCl solution, respectively. Tumor net weight was measured and survival time was observed. Microvessel density within tumor tissues was determined by CD31 immunohistochemistry. H&E staining of lungs and TUNEL assay of primary tumor tissues were also conducted. The results displayed that pSecTag2B-vasostatin could inhibit the growth and metastasis of hepatocellular carcinoma xenografts and prolong survival time compared with the controls in vivo. Moreover, histologic analysis revealed that pSecTag2B-vasostatin treatment increased apoptosis and inhibited angiogenesis. The present data may be of importance to the further exploration of this new anti-angiogenesis approach in the treatment of hepatocellular cancer.
实体瘤的生长和转移依赖于血管生成。抗血管生成治疗可能是一种有前景的治疗选择。血管抑素是钙网蛋白的N端结构域，是一种非常有效的血管生成和肿瘤生长的内源性抑制剂。在本研究中，我们试图研究编码血管抑素的质粒与阳离子脂质体复合后是否能在体内抑制肝细胞癌的生长和转移，并发现其可能的作用机制。通过体外流式细胞术分析检测pSecTag2B-血管抑素质粒对小鼠内皮细胞（MS1）的凋亡诱导作用。荷HCCLM3肿瘤的裸鼠分别接受pSecTag2B-血管抑素、pSecTag2B空载体和0.9%氯化钠溶液。测量肿瘤净重并观察生存时间。通过CD31免疫组织化学测定肿瘤组织内的微血管密度。还进行了肺组织的苏木精-伊红染色和原发性肿瘤组织的TUNEL检测。结果显示，与体内对照组相比，pSecTag2B-血管抑素可抑制肝细胞癌异种移植瘤的生长和转移，并延长生存时间。此外，组织学分析显示，pSecTag2B-血管抑素治疗可增加凋亡并抑制血管生成。本研究数据可能对进一步探索这种新的抗血管生成方法治疗肝细胞癌具有重要意义。
