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产芽孢梭菌蛋氨酸γ裂解酶增强阿霉素在 A549 细胞和人源异种移植瘤中的抗癌作用。

Methionine gamma lyase from Clostridium sporogenes increases the anticancer effect of doxorubicin in A549 cells and human cancer xenografts.

机构信息

Laboratory of Combined Treatment, Laboratory of Cell Immunity, N.N. Blokhin Cancer Research Center, Moscow, Russia.

Department of Biochemistry, Peoples' Friendship University of Russia (RUDN University), Moscow, Russia.

出版信息

Invest New Drugs. 2019 Apr;37(2):201-209. doi: 10.1007/s10637-018-0619-4. Epub 2018 Jun 15.

DOI:10.1007/s10637-018-0619-4
PMID:29948359
Abstract

The anti-cancer efficacy of methionine γ-lyase (MGL) from Clostridium sporogenes (C. sporogenes) is described. MGL was active against cancer models in vitro and in vivo. The calculated EC50 values for MGL were 4.4 U/ml for A549, 7.5 U/ml for SK-BR3, 2.4 U/ml for SKOV3, and 0.4 U/ml for MCF7 cells. The combination of doxorubicin (DOX) and MGL was more effective for A549 human lung cancer growth inhibition than either agent alone in vitro and in vivo. MGL reduced the EC50 of doxorubicin from 35.9 μg/mL to 0.01-0.265 μg/mL. The growth inhibitory effect of DOX + MGL on A549 xenografts in vivo was reflective of the results obtained in vitro. The inhibition rate of tumor growth in the combined arm was 57%, significantly higher than that in the doxorubicin (p = 0.033)-alone arm.

摘要

本文描述了来自生孢梭菌(C. sporogenes)的蛋氨酸 γ-裂解酶(MGL)的抗癌功效。MGL 在体外和体内对癌症模型均具有活性。MGL 对 A549、SK-BR3、SKOV3 和 MCF7 细胞的 EC50 值分别为 4.4 U/ml、7.5 U/ml、2.4 U/ml 和 0.4 U/ml。与单独使用任一药物相比,阿霉素(DOX)和 MGL 的联合使用对 A549 人肺癌的生长抑制作用在体外和体内均更为有效。MGL 将阿霉素的 EC50 从 35.9μg/mL 降低至 0.01-0.265μg/mL。DOX+MGL 对 A549 异种移植物的体内生长抑制作用反映了体外获得的结果。联合组的肿瘤生长抑制率为 57%,明显高于阿霉素(p=0.033)单一组。

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