去甲斑蝥素对人胆囊癌裸鼠移植瘤的体内抗肿瘤机制

[Anti-tumor mechanism of norcantharidin for the implanted tumors of human gallbladder carcinoma in nude mice in vivo].

作者信息

Fan Yue-zu, Zhao Ze-ming, Fu Jin-ye, Chen Chun-qiu

机构信息

Department of Surgery, Tongji Hospital of Tongji University, Shanghai 200065, China.

出版信息

Zhonghua Wai Ke Za Zhi. 2006 May 1;44(9):618-22.

PMID:16784656

Abstract

OBJECTIVE

To explore the anti-tumor mechanism of norcantharidin (NCTD) for the implanted tumors of human gallbladder carcinoma in nude mice in vivo.

METHODS

Animal model of implanted tumors of human gallbladder carcinoma in nude mice was established. Mice were randomly divided into control, 5-FU, NCTD and NCTD + 5-FU groups and were taken different treatment. The expressions of PCNA, Ki-67, cyclin D1, p27, Bcl-2, Bax, Survivin, nm23/nm23-H1, MMP2 and TIMP2 proteins or genes in each tissue section of every group were determined by immunohistochemistry and RT-PCR.

RESULTS

(1) On proliferation-related gene proteins, the expression of PCNA, Ki-67, cyclin D1 was significantly decreased, with significantly increased expression of p27 protein, in paraffin sections of NCTD group when compared with control group (P < 0.05); The expression of PCNA mRNA, cyclin D1 mRNA was decreased, with significantly increased expression of p27 mRNA in NCTD group. (2) On apoptosis-related gene proteins, the expression of Bcl-2 was significantly decreased in paraffin sections of NCTD group when compared with control group (P < 0.05); The expression of Bcl-2 mRNA, Survivin mRNA was significantly decreased, with significantly increased expression of Bax mRNA in NCTD group. (3) There was significant difference on invasion around tumor and lung metastasis in NCTD group when compared with control group (P < 0.01). On metastasis-related gene proteins, the expression of nm23 and TIMP2 was significantly increased, with significantly decreased expression of MMP2 in paraffin sections of NCTD group when compared with control group (P < 0.05); The expression of nm23-H1 mRNA, TIMP2 mRNA was significantly increased, with significantly decreased expression of MMP2 mRNA in NCTD group.

CONCLUSIONS

The anti-tumor mechanism of NCTD for human gallbladder carcinoma in nude mice might correlated with inhibition of cell proliferation, blockage of cell cycle, induction of cell apoptosis, reducing of cell motility and invasive capability, alteration of the expression of proliferation-, apoptosis- and metastasis-related gene proteins such as PCNA, Ki-67, cyclin D1, p27, Bcl-2, Bax, Survivin, nm23, MMP2 and TIMP2.

摘要

目的

探讨去甲斑蝥素（NCTD）对人胆囊癌裸鼠移植瘤的体内抗肿瘤机制。

方法

建立人胆囊癌裸鼠移植瘤动物模型。将小鼠随机分为对照组、5-氟尿嘧啶组、NCTD组和NCTD + 5-氟尿嘧啶组，并给予不同治疗。通过免疫组织化学和逆转录-聚合酶链反应（RT-PCR）检测每组各组织切片中PCNA、Ki-67、细胞周期蛋白D1、p27、Bcl-2、Bax、Survivin、nm23/nm23-H1、基质金属蛋白酶2（MMP2）和金属蛋白酶组织抑制因子2（TIMP2）蛋白或基因的表达。

结果

（1）在增殖相关基因蛋白方面，与对照组相比，NCTD组石蜡切片中PCNA、Ki-67、细胞周期蛋白D1的表达显著降低，p27蛋白表达显著增加（P < 0.05）；NCTD组PCNA mRNA、细胞周期蛋白D1 mRNA表达降低，p27 mRNA表达显著增加。（2）在凋亡相关基因蛋白方面，与对照组相比，NCTD组石蜡切片中Bcl-2的表达显著降低（P < 0.05）；NCTD组Bcl-2 mRNA、Survivin mRNA表达显著降低，Bax mRNA表达显著增加。（3）与对照组相比，NCTD组肿瘤周围浸润和肺转移有显著差异（P < 0.01）。在转移相关基因蛋白方面，与对照组相比，NCTD组石蜡切片中nm23和TIMP2的表达显著增加，MMP2的表达显著降低（P < 0.05）；NCTD组nm23-H1 mRNA、TIMP2 mRNA表达显著增加，MMP2 mRNA表达显著降低。