蛋白酶抑制剂leupeptin增强抗肿瘤药物对肿瘤细胞的增殖抑制作用  

Protease Inhibitor Leupeptin Enhances the Inhibitory Effect of Anticancer Drugs on the Proliferations of Cancer Cells

作　　者：王莹[1] 吴淑英[1] 甄永苏[1] 

机构地区：[1]中国医学科学院/北京协和医学院医药生物技术研究所,100050

出　　处：《医学研究杂志》2012年第10期56-60,共5页Journal of Medical Research

摘　　要：目的研究蛋白酶抑制剂(protease inhibitor)leupeptin对化疗药物紫杉醇(taxol,TAX)、吉西他滨(gemcitabine,GEM)以及平阳霉素(pingyangmycin,PYM)在体外抑制肿瘤细胞增殖作用的影响。方法选取一定浓度梯度的酶抑制剂leupep-tin单独或联合TAX、GEM和PYM与肿瘤细胞孵育,48h后采用MTT法测定肿瘤细胞生长的变化并与相应浓度的TAX、GEM和PYM单药组相比较。采用流式细胞术测定MCF-7细胞周期分布。结果 leupeptin在浓度高于50μmol/L时可增强化疗药物对肺癌PG细胞和乳腺癌MCF-7细胞增殖的抑制作用。leupeptin对TAX的增效作用尤为显著。leupeptin与低浓度的GEM和TAX联合应用可改变MCF-7的细胞周期分布。结论 leupeptin可增强化疗药物对肿瘤细胞增殖的抑制作用,但其作用程度与肿瘤细胞株的种类、化疗药物的种类及leupeptin的浓度均相关。Objective To observe the modulating effect of leupeptin, a protease inhibitor, on the anti - proliferation efficacy of anti- cancer drugs including taxol （TAX） , gemcitabine （GEM） , and pingyangmycin （PYM） in cancer cells. Methods Mammary carcinoma MCF -7 cells and pulmonary carcinoma PG cells were exposed to various concentrations of leupeptin alone or in combination with taxol （TAX）, gemcitabine （EM）, and pingyangmycin （PYM）, respectively. After 48 hours exposure, cell proliferation was determined by MTT assay. Flow cytometry was used to analyze cell cycle distribution. Results At the concentration of 50p^mol/L or higher, leupeptin enhanced the inhibitory effect of those three anticancer drugs on the proliferation of both cell line. More marked enhancement was found in the combination of leupeptin and TAX. MCF - 7 cell cycle distributions were changed at the low dosage GEM or TAX combination with le- upeptin. Conclusion Leupeptin could enhance the inhibition effect of anticancer drugs, in particular, taxol, on cancer cells. The effica- cy may be varied in different cell lines and drugs.

关 键 词：LEUPEPTIN MCF-7细胞 PG细胞 增殖抑制 

分 类 号：R739.5[医药卫生—肿瘤]