维拉帕米对Lewis肺癌的抑制作用以及对MMP-9表达的影响

Inhibitive efficacy of verapamil on Lewis lung cancer and its effect on the expression of MMP-9

目的研究维拉帕米对Lewis肺癌的抑制作用以及对其基质金属蛋白酶-9(MMP-9)表达的影响。方法建立Lewis肺癌模型,将其分为4组:A组为空白对照组,B、C、D组分别为维拉帕米0.15、0.20和0.25mg·d-1剂量组。采用ELISA方法检测各组小鼠血清中MMP-9的浓度,采用免疫组化DakoEnVison二步法证实瘤组织中MMP-9的存在,并计数肺表面转移结节数,瘤块称重。结果MMP-9浓度与肺表面转移结节数、瘤重存在一定的相关性,且当维拉帕米剂量为0.25或0.20mg·d-1时,维拉帕米能明显降低小鼠血清中MMP-9的浓度(P<0.05),同时肿瘤生长和转移作用也受到明显的抑制。但0.25mg·d-1的剂量有可能引起一定的不良反应。结论维拉帕米对Lewis肺癌有一定的抑制作用,且可能通过抑制MMP-9而抑制了肿瘤的生长和转移。

AIM To study the inhibitive effeet of verapamil on matrix metalloproteinase-9 （MMP-9）of Lewis lung carcinoma model, investigate suppressive effect of verapamil on Lewis lung carcinoma. METHODS The Lewis lung earcinoma model was established and divided into 4 groups： group A was the eontrol group, group B was treated with verapamil with a dose of 0.15 nag·d^-1, group C was treated with a dose of 0.20 mg·d^-1, and group D was treated with a dose of 0.25 mg· d^- 1. Through the technique of ELISA, the concentration of MMP-9 in serum of treated groups and control group was detected. EnVision immunohistoehemieal technique was used to detect the expression of MMP-9 in Lewis lung cancer tissue. Then, to value the tumor-suppressing effect of verapamil, the inhibition rate of eaneer spontaneous metastasis and local invasion of these groups was ealeulated. The correlation analysis between MMP-9 concentration and tumor weight, that between MMP-9 concentration and number of metastasis, were both provided. RESULTS There was correlation between MMP-9 concentration and tumor weight（ R-squared = 0. 697 4）, also between MMP-9 concentration and number of metastasis （ R-squared 0.539 5）. There was a significant reduction of serum MMP-9 on group C and D （ P 〈 0.05）, and eonspieuous inhibition of spontaneous metastasis and local invasion （The inhibition rate of eaneer spontaneous metastasis of group D reached to 51.9 %, and that of local invasion of group D reached to 44.4 % ）. But thehair removing phenomenon was observed in group D with a high dose of vempamil. CONCLUSION There is a significant tumor-suppressing effect of verapamil on Lewis lung carcinoma, and this effect may result from its inhibiting MMPs, and through further researches, vempamil is expected to be used in lung cancer treatment.