去甲斑蝥素对荷瘤裸鼠胆囊癌移植瘤nm23、基质金属蛋白酶-2和基质金属蛋白酶组织抑制因子-2的影响

目的探讨去甲斑蝥素(NCTD)对荷瘤裸鼠胆囊癌移植瘤nm23、基质金属蛋白酶(MMP)2和基质金属蛋白酶组织抑制因子(TIMP)2的影响。方法在培养人胆囊癌GBCSD细胞的基础上建立荷瘤鼠胆囊癌模型并进行移植瘤抑制实验,实验分为空白对照、5氟脲嘧啶(FU)、NCTD、NCTD+5FU4组,观测荷瘤鼠移植瘤大小改变、抑瘤率和细胞nm23、MMP2、TIMP2蛋白表达。结果NCTD对荷瘤鼠胆囊癌移植瘤有明显的抑制作用;NCTD组呈棕褐MMP2染色的细胞明显减少,胞浆着色变淡,表达率显著降低(P<0.05);而呈nm23、TIMP2表达棕褐染色的细胞数明显增多,胞浆着色变深、变浓,表达率显著增高(P<0.05);其中均以NCTD+5FU组的作用最明显(P<0.05)。结论NCTD可明显抑制人胆囊癌的侵袭和转移,若与5FU联合应用则具协同作用。其机制可能与NCTD影响转移和基质溶解相关基因蛋白表达有关。

In vivo effect of norcantharidin on expression of metastasis-related gene proteins such as nm23,MMP-2 and TIMP-2 of implanted tumor cells of human gallbladder carcinoma in nude mice

Objective To study the influence of norcantharidin on the expression of metastasis-related gene proteins such as nm23,MMP-2 and TIMP-2 of implanted tumor cells of human gallbladder carcinoma in nude mice in vivo.Methods Human gallbladder carcinoma GBC-SD cells were cultured by cell culture technique.Tumor model of human gallbladder carcinoma was established by subcutaneous implantation of cultured GBC-SD cells into nude mice.Mice used in experiments were randomly divided into control,5-FU,NCTD and NCTD+5-FU groups and were subjected to different treatments.Tumor dimension,tumor inhibitory rate in each group and the expression of nm23,MMP-2,TIMP-2 gene proteins determined by streptavidin-biotin complex method in each paraffin section of every implanted tumor in nude mice were evaluated simultaneously.Results Volume of implanted tumors (5.61+0.39 cm3 vs 9.78+0.61 cm3,P<0.05) in nude mice in NCTD group was smaller than that in control group,but tumor inhibitory rate was increased (42.63% vs 0,P<0.05).The expression of MMP-2 was significantly decreased and the expression of nm23 and TIMP-2 was significantly increased in paraffin sections of NCTD group (P<0.05).Moreover,there was significant difference in tumor volume (4.51+1.11 cm3),tumor inhibitory rate (52.89%) and the expression of above-mentioned gene proteins in NCTD+5-FU group as compared with other groups (P<0.05).Conclusion NCTD inhibits the invasion and metastasis of implanted tumor cells of human gallbladder carcinoma in nude mice in vivo.Its anti-invasive activity may be the results of influence in expression of metastasis-related gene proteins such as nm23,MMP-2 and TIMP-2.