增殖、血管生成和凋亡相关蛋白是乙醇提取物罗勒叶对MNNG诱导的胃癌发生进行化学预防的分子靶点。

Proliferation, angiogenesis and apoptosis-associated proteins are molecular targets for chemoprevention of MNNG-induced gastric carcinogenesis by ethanolic Ocimum sanctum leaf extract.

作者信息

Manikandan P, Vidjaya Letchoumy P, Prathiba D, Nagini S

机构信息

Department of Biochemistry and Biotechnology, Faculty of Science, Annamalai University, Annamalainagar 608002, Tamil Nadu, India.

出版信息

Singapore Med J. 2007 Jul;48(7):645-51.

PMID:17609827

Abstract

INTRODUCTION

This study was designed to evaluate the chemopreventive effects of ethanolic Ocimum sanctum (OS) leaf extract on cell proliferation, apoptosis and angiogenesis during N-methyl-N'-nitro-N-nitrosoguanidine (MNNG)-induced gastric carcinogenesis.

METHODS

The rats were divided into four groups of ten each. Rats in group one were given MNNG (150 mg/kg body weight) by intragastric intubation three times, with a two-week interval between treatments. Rats in group two were administered MNNG as in group one, and in addition, they received intragastric intubation of ethanolic OS extract (300 mg/kg body weight) three times per week, starting on the day following the first exposure to MNNG. The intubation of ethanolic OS extract continued until the end of the experimental period. Rats in group three were given ethanolic OS leaf extract only. Group four served as controls. All the rats were killed after an experimental period of 26 weeks.

RESULTS

Intragastric administration of MNNG-induced well-differentiated squamous cell carcinomas that showed increased cell proliferation, and angiogenesis with evasion of apoptosis, as revealed by the upregulation of proliferating cell nuclear antigen (PCNA), glutathione S-transferase-pi (GST-pi), Bcl-2, cytokeratin (CK) and vascular endothelial growth factor (VEGF) and with downregulation of Bax, cytochrome C and caspase 3 protein expression. Administration of ethanolic OS leaf extract reduced the incidence of MNNG-induced gastric carcinomas. This was accompanied by decreased expression of PCNA, GST-pi, Bcl-2, CK and VEGF, and overexpression of Bax, cytochrome C, and caspase 3.

CONCLUSION

This study provides evidence that, in MNNG-induced gastric carcinogenesis, the key proteins involved in the proliferation, invasion, angiogenesis and apoptosis, are viable molecular targets for chemoprevention using ethanolic OS leaf extract.

摘要

引言

本研究旨在评估乙醇提取物罗勒叶（OS）对N-甲基-N'-硝基-N-亚硝基胍（MNNG）诱导的胃癌发生过程中细胞增殖、凋亡和血管生成的化学预防作用。

方法

将大鼠分为四组，每组十只。第一组大鼠通过胃内插管给予MNNG（150mg/kg体重），共三次，每次给药间隔两周。第二组大鼠给予与第一组相同剂量的MNNG，此外，从首次接触MNNG后的第二天开始，每周通过胃内插管给予乙醇提取物罗勒叶（300mg/kg体重）三次。乙醇提取物罗勒叶的插管持续至实验期结束。第三组大鼠仅给予乙醇提取物罗勒叶。第四组作为对照组。在26周的实验期后，处死所有大鼠。

结果

胃内给予MNNG诱导了高分化鳞状细胞癌，表现为细胞增殖增加、血管生成以及凋亡逃避，这通过增殖细胞核抗原（PCNA）、谷胱甘肽S-转移酶-pi（GST-pi）、Bcl-2、细胞角蛋白（CK）和血管内皮生长因子（VEGF）的上调以及Bax、细胞色素C和半胱天冬酶3蛋白表达的下调得以揭示。给予乙醇提取物罗勒叶降低了MNNG诱导的胃癌发生率。这伴随着PCNA、GST-pi、Bcl-2、CK和VEGF表达的降低，以及Bax、细胞色素C和半胱天冬酶3的过表达。