Takahashi Y, Niitsu Y
Dept. of Internal Medicine, Sapporo Medical University School of Medicine.
Gan To Kagaku Ryoho. 1994 Jun;21(7):945-51.
It has been known that many drug resistant factors including p-glycoprotein related to anticancer drug resistance. It is assumed that Glutathione s-transferase (GST) is one of the resistant factors. In this present study, we examined the relationship between GST (especially GST-pi) and drug resistance, and also possibility of overcoming of drug resistance for GST-pi related drug resistance. We studied whether GST-pi directly related to anticancer drug resistance by transfection of GST-pi antisense cDNA into human colonic cancer cell line (M 7609). By transfection, cytosolic GST-pi concentrations decreased and sensitivity for adriamycin increased. It was confirmed that GST-pi directly related to some anticancer drug resistance including adriamycin. Moreover, we also have found that ketoprofen, which is an inhibitor of GST-pi activity, increased Adriamycin sensitivity. That is, partial overcoming of drug resistance was obtained. In future, it will be expected that GST-pi inhibitors etc are tried for overcoming of drug resistance.
已知许多耐药因素,包括与抗癌药物耐药性相关的P-糖蛋白。据推测,谷胱甘肽S-转移酶(GST)是耐药因素之一。在本研究中,我们研究了GST(尤其是GST-π)与耐药性之间的关系,以及克服与GST-π相关的耐药性的可能性。我们通过将GST-π反义cDNA转染到人结肠癌细胞系(M7609)中,研究了GST-π是否与抗癌药物耐药性直接相关。通过转染,胞质GST-π浓度降低,对阿霉素的敏感性增加。证实GST-π与包括阿霉素在内的某些抗癌药物耐药性直接相关。此外,我们还发现,作为GST-π活性抑制剂的酮洛芬增加了阿霉素的敏感性。也就是说,实现了耐药性的部分克服。未来,有望尝试使用GST-π抑制剂等来克服耐药性。