蝎毒多肽提取物（PESV）联合化疗对Lewis肺癌血管生成的抑制作用

[Effect of polypeptide extract from scorpion venom (PESV) with chemotherapy inhibited angiogenesis of Lewis lung carcinomas].

作者信息

Sun Xiaojia, Zhang Yueying, Jia Qing, Wang Zhaopeng, Wang Zhaoxia, Zhang Weidong

机构信息

Department of Experimental Pathology and Pathophysiology, Institute of Basic Medicine, Shandong Academy of Medical Sciences, Key Laboratory of Monder Medicine and Technology of Shandong Province, Jinan 250062, China.

出版信息

Zhongguo Zhong Yao Za Zhi. 2011 Jun;36(12):1644-9.

PMID:22007553

Abstract

OBJECTIVE

To study the effects of polypeptide extract from scorpion venom (PESV) alliance with chemotherapy on angiogenesis of Lewis lung carcinomas (LLC) and its mechanism.

METHOD

LLC cells suspension (4 x 10(6) cells/mL) were subcutaneously injected into 54 C57BL/6J mice in right armpits. Then the tumor-bearing mice were randomly divided into three groups: the control group, the chemotherapy group and the PESV group. Cyclophosphamide was used to establish the model of cancer. Chemotherapy and PESV were added to the PESV group. Every 7 days, 6 mice of each group were executed, and the experiments were carried out for 28 days. The tumor volume and inhibitory rate were determined. Immunohistochemistry and RT-PCR were used to determine the expression of factor VIII, alpha-SMA, Dll4 and Notch1 in tumor tissue. Correlation analysis was used to identify the relationship of factor VIII and calculate microvessel density (MVD), alpha-SMA and vascular maturity.

RESULT

The inhibitory rate of PESV was 42.21%. Comparing with the chemotherapy group, the expression of tumor factor Dll4 and Notch1 in the PESV group were decreased significantly (P < 0.05). The expression of factor VIII and alpha-SMA in the chemotherapy group is lower than the control group (P < 0.05), while it's higher when compared with the PESV group (P < 0.01). Expression of Dll4 and Notch1 in the chemotherapy group at the 28th day were higher than the control group (P < 0.05), and the expression in the PESV group at the 21st day were significantly lower than the chemotherapy group (P < 0.05).

CONCLUSION

PESV could inhibit the angiogenesis of LLC. It might be attained by decreasing the level of angiogenic factors, that are factor VIII, alpha-SMA, Dll4 and Notch1 in tumor microenvironment.

摘要

目的

研究蝎毒多肽提取物（PESV）联合化疗对Lewis肺癌（LLC）血管生成的影响及其机制。

方法

将LLC细胞悬液（4×10⁶个细胞/mL）皮下注射到54只C57BL/6J小鼠的右腋窝。然后将荷瘤小鼠随机分为三组：对照组、化疗组和PESV组。用环磷酰胺建立癌症模型。化疗组加入化疗药物，PESV组加入化疗药物和PESV。每组每7天处死6只小鼠，实验持续28天。测定肿瘤体积和抑制率。采用免疫组织化学和RT-PCR法检测肿瘤组织中因子VIII、α-SMA、Dll4和Notch1的表达。采用相关性分析确定因子VIII与微血管密度（MVD）、α-SMA与血管成熟度的关系。

结果

PESV的抑制率为42.21%。与化疗组相比，PESV组肿瘤因子Dll4和Notch1的表达明显降低（P<0.05）。化疗组因子VIII和α-SMA的表达低于对照组（P<0.05），但高于PESV组（P<0.01）。化疗组第28天Dll4和Notch1的表达高于对照组（P<0.05），PESV组第21天的表达明显低于化疗组（P<0.05）。