新型基质金属蛋白酶抑制剂MMI-166对裸鼠胰腺癌移植瘤作用的研究  

Effects of a new matrix metalioproteinase inhibitor, MMI-166, in nude mouse xenografts of human pan-creatic cancer XU Huai-yong

作　　者：徐怀勇[1] 巩本刚[1] 高崇崇 李梦字[1] 吴俊本[1] 相亭海[1] 成丕光[1] 

机构地区：[1]滨州医学院附属滨州市人民医院肝胆外科,256600 [2]滨州医学院临床学院

出　　处：《中华肝胆外科杂志》2012年第11期859-862,共4页Chinese Journal of Hepatobiliary Surgery

基　　金：山东省科技发展计划项目（2009GG20002096）

摘　　要：目的观察新型选择性基质金属蛋白酶（MMP）抑制剂MMI-166对裸鼠人胰腺癌细胞SWl990移植瘤生长及瘤内MMP-2、MMP-9蛋白表达和细胞凋亡的影响。方法应用人胰腺癌细胞株SWl990建立裸鼠胰腺癌皮下移植瘤模型。裸鼠随机分为对照组和实验组。对照组口服生理盐水，实验组口服MMI-166（200mg·kg^-1·d^-1）。游标卡尺测量肿瘤的长、短径，比较两组间肿瘤体积、抑瘤率。采用免疫组织化学测定肿瘤组织内MMP-2、MMP-9蛋白的表达。利用脱氧核苷酸末端转移酶介导缺口末端标记法（TUNEL法）检测细胞凋亡指数（AI）。结果研究结束后，实验组移植瘤肿瘤体积为（1252．30±464．84）mm^3，明显小于对照组移植瘤肿瘤的（2241．82±208．06）min^3；实验组瘤体重（1．42±0．15）g，低于对照组的瘤体重[（2．17±0．20）g]；实验组抑瘤率为34．47％。实验组内蛋白MMP-2和MMP-9的表达分别为（2．80±1．10）、（2，60±1．52），与对照组相比显著降低；细胞凋亡指数在实验组为（75．60±9．71）％，显著高于对照组的（17．40±10．14）％。结论MMI-166可抑制胰腺癌肿瘤的生长并诱导细胞凋亡，其机制可能与抑制MMP-2、MMP-9蛋白表达有关。Objective To investigate of the MMI-166 on the expression of MMP-2, MMP-9 and the cell apoptosis of nude mouse xenografts of SW1990 human pancreatic cancer cells. Methods Es- tablishment of control and experimental groups, randomly, the human pancreatic cancer xenograft model of SW1990 was constructed. The control group was treated with normal saline, and experimen- tal group was treated with MMI-166 （200 mg·kg^-1·d^-1）. The tumor volume and tumor inhibition rate was measured by vernier caliper through length and short diameter. The expression of MMP-2 and MMP-9 protein was observed using immunohistochemistry in the tumor tissues. Apoptosis index was detected by deoxynucleotidyl transferase-mediated nick end labeling （TUNEL method）. Results The tumor volume of MMI-166 group （1252. 30±464.84） mm3 was less than the control group （2241. 82±208.06） mm^3, significantly. The inhibition rate was 34. 47% between the experimental groups （treat with MMI 166） （1.42±0.15） g and control group （2. 17±0.20） g. The expression of MMP-2 （2.80 ±1.10） % and MMP-9 （2.60±1.52）%protein was significantly downregulated in MMI-166 group, compared with the control group. Apoptotic index in the experimental group （75.60±9.71） % was higher than the control group （17.40±10.14）%, significantly. Conclusion The mechanism of MMI 166 inhibiting pancreatic tumor growth and inducing apoptosis may be related to the suppression of MMP-2 and MMP-9 protein expression.

关 键 词：胰腺肿瘤 蛋白酶抑制药 基质金属蛋白酶 细胞凋亡 

分 类 号：R735.9[医药卫生—肿瘤]