通过阿霉素暴露建立多药耐药大鼠腹水肝癌AH130细胞系，该细胞系显示出低DT-黄递酶活性以及对丝裂霉素的高交叉耐药性。

Establishment by adriamycin exposure of multidrug-resistant rat ascites hepatoma AH130 cells showing low DT-diaphorase activity and high cross resistance to mitomycins.

作者信息

Wakusawa S, Nakamura S, Miyamoto K

机构信息

Faculty of Pharmaceutical Sciences, Hokuriku University, Kanazawa.

出版信息

Jpn J Cancer Res. 1997 Jan;88(1):88-96. doi: 10.1111/j.1349-7006.1997.tb00306.x.

DOI:10.1111/j.1349-7006.1997.tb00306.x

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5921242/

Abstract

A resistant subline (AH130/5A) selected from rat hepatoma AH130 cells after exposure to adriamycin (ADM) showed remarkable resistance to multiple antitumor drugs, including mitomycin C (MMC) and porfiromycin (PFM). PFM, vinblastine (VLB), and ADM accumulated in AH130/5A far less than in the parent AH130 (AH130/P) cells. AH130/5A cells showed overexpression of P-glycoprotein (PGP), an increase in glutathione S-transferase activity, and a decrease in DT-diaphorase and glutathione peroxidase activity. The resistance to MMC and VLB of AH130/5A cells was partly reversed by H-87, an inhibitor of PGP. Buthionine sulfoximine, an inhibitor of glutathione synthase, did not affect the action of MMC. tert-Butylhydroquinone induced DT-diaphorase activity, increased PFM uptake, and enhanced the growth-inhibitory action of MMC in AH130/5A cells. Dicumarol, an inhibitor of DT-diaphorase, decreased PFM uptake and reduced the growth-inhibitory action of MMC in AH130/P cells. These results indicated that the adriamycin treatment of hepatoma cells caused multifactorial multidrug resistance involving a decrease in DT-diaphorase activity.

摘要

从大鼠肝癌AH130细胞经阿霉素（ADM）处理后筛选出的耐药亚系（AH130/5A）对多种抗肿瘤药物表现出显著耐药性，包括丝裂霉素C（MMC）和卟吩姆钠（PFM）。PFM、长春碱（VLB）和ADM在AH130/5A细胞中的蓄积远低于亲本AH130（AH130/P）细胞。AH130/5A细胞显示P-糖蛋白（PGP）过表达、谷胱甘肽S-转移酶活性增加以及DT-黄递酶和谷胱甘肽过氧化物酶活性降低。AH130/5A细胞对MMC和VLB的耐药性部分被PGP抑制剂H-87逆转。谷胱甘肽合酶抑制剂丁硫氨酸亚砜胺不影响MMC的作用。叔丁基对苯二酚诱导DT-黄递酶活性，增加PFM摄取，并增强MMC对AH130/5A细胞的生长抑制作用。DT-黄递酶抑制剂双香豆素降低PFM摄取并降低MMC对AH130/P细胞的生长抑制作用。这些结果表明，对肝癌细胞进行阿霉素处理会导致多因素多药耐药，其中包括DT-黄递酶活性降低。

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