【摘要】 目的：探讨去甲斑蝥素(norcantharidin,NCTD)对人原发性胆囊癌侵袭和转移的影响及其机制。方法：应用细胞培养技术培养人原发性胆囊癌GBC-SD细胞,通过建立裸鼠人胆囊癌移植瘤模型进行随机药物体内实验,实验分为空白(生理盐水)对照组、5-FU组、NCTD组、5-FU+NCTD组4组,观察荷瘤裸鼠移植瘤的瘤周组织浸润和肺转移；同时应用免疫组化SABC法检测NCTD对移植瘤细胞中nm23、MMP-2、TIMP-2蛋白表达的影响。结果：在动物实验中,NCTD可明显减少荷瘤裸鼠移植瘤的瘤周组织浸润和肺转移瘤结节(P＜0.05)；免疫组化检测显示NCTD组MMP-2表达下降,nm23、TIMP-2表达上升(P＜0.05)；若与5-FU联合应用上述作用更明显。结论：在裸鼠人胆囊癌模型中,NCTD可明显抑制人胆囊癌的侵袭和转移,若与5-FU联合应用则具协同作用,其机制可能与NCTD影响基质溶解和转移相关基因表达有关。更多还原

【Abstract】 Objective:To study the inhibitory effects of norcantharidin (NCTD) on invasion and metastasis of human gall- bladder carcinomas in vivo and corresponding mechanism.Methods:Human primary gallbladder carcinoma GBC-SD cells were cultured by cell culture technique.Xenograft model of human gallbladder carcinoma was established by subcutaneous implanta- tion of cultured GBC-SD cells into nude mice.Nude mice were randomly divided into four groups:control group (normal saline), 5-fluorouracil (5-FU) group,NCTD group,and 5-FU+NCTD group.Tissue invasion around tumor ceils and lung metastasis were observed.The expressions of nm23 (non-metastasis),metalloproteinases-2 (MMP-2),and tissue inhibitor of metallopro- teinases-2 (TIMP-2) protein were determined by immunohistochemical streptavidin-biotin complex (SABC) method.Results: NCTD significantly reduced tissue invasion around tumor cells and lung metastasis compared with control (P＜0.05).The ex- pression of MMP-2 was significantly decreased and the expression of nm23 and TIMP-2 were significantly increased in NCTD—treated group (P＜0.05).5-FU had the synergistic effects with NCTD (P＜0.05).Conclusion:NCTD can inhibit the invasion and metastasis of human gallbladder carcinomas in nude mice.5-FU had the synergistic effects with NCTD.The mechanism may correlate with the effects of NCTD on MMP-2,nm23,and TIMP-2 protein expression.更多还原