Kawamoto S, Deguchi T, Nezesa S, Yamada S, Okano M, Kawada Y
Department of Urology, Gifu University School of Medicine, Japan.
Urol Res. 1997;25(6):407-12. doi: 10.1007/BF01268857.
We have demonstrated that low-level expression of P-glycoprotein (PGP), detectable by reverse transcriptase polymerase chain reaction (RT-PCR) assay and flow cytometric assay, is an important factor in multidrug resistance (MDR) in ACHN cancer cells. In this study, we established a subline highly resistant to adriamycin (ACHN/ADM) from ACHN cells, and determined the correlation between PGP levels and MDR levels using ACHN/ADM cells and their parent ACHN cells. The ACHN/ADM cells showed overexpression of PGP, and sensitivity to antitumor agents was lower than that found in ACHN cells. Intracellular accumulation of ADM in ACHN/ADM cells was approximately half the amount of its accumulation in ACHN cells. Sensitivity to ADM in ACHN/ADM cells was enhanced by chemosensitizers with an increase in intracellular ADM accumulation. These results indicate that PGP levels correlate with MDR levels and suggest that chemotherapy using chemosensitizers might be effective in the treatment of renal cancers with overexpression of PGP.
我们已经证明,通过逆转录聚合酶链反应(RT-PCR)检测法和流式细胞术检测法可检测到的P-糖蛋白(PGP)低水平表达是ACHN癌细胞多药耐药(MDR)的一个重要因素。在本研究中,我们从ACHN细胞中建立了对阿霉素高度耐药的亚系(ACHN/ADM),并使用ACHN/ADM细胞及其亲代ACHN细胞确定了PGP水平与MDR水平之间的相关性。ACHN/ADM细胞表现出PGP的过表达,并且其对抗肿瘤药物的敏感性低于ACHN细胞。阿霉素在ACHN/ADM细胞中的细胞内蓄积量约为其在ACHN细胞中蓄积量的一半。具有细胞内阿霉素蓄积量增加的化学增敏剂增强了ACHN/ADM细胞对阿霉素的敏感性。这些结果表明PGP水平与MDR水平相关,并提示使用化学增敏剂进行化疗可能对治疗PGP过表达的肾癌有效。