Roberts D, Meyers M B, Biedler J L, Wiggins L G
Department of Biochemical and Clinical Pharmacology, St. Jude Children's Research Hospital, Memphis, Tennessee 38101.
Cancer Chemother Pharmacol. 1989;23(1):19-25. doi: 10.1007/BF00258452.
L1210 sublines independently selected for resistance to teniposide (VM-26), etoposide (VP-16), doxorubicin (DOX), dactinomycin (DACT), or vincristine (VCR) express an anionic, 22-kDa protein that is not observed in extracts of parental L1210 cells. Antibody raised against sorcin, an acidic calcium-binding protein overproduced in many other cells resistant to these agents, cross-reacts with the 22-kDa polypeptide. The levels of the 22-kDa protein (sorcin) increase with the relative levels of drug resistance of the L1210 sublines. The appearance of sorcin in these various sublines further supports the notion that the overproduction of this protein is related to the general phenomenon of multidrug resistance rather than to specific drug resistance and that selection for resistance to teniposide produces L1210 sublines with multidrug resistance.
独立筛选出的对替尼泊苷(VM - 26)、依托泊苷(VP - 16)、阿霉素(DOX)、放线菌素D(DACT)或长春新碱(VCR)具有抗性的L1210亚系表达一种阴离子型22 kDa蛋白,而在亲本L1210细胞提取物中未观察到这种蛋白。针对索辛(sorcin)产生的抗体与这种22 kDa多肽发生交叉反应,索辛是一种在许多其他对这些药物具有抗性的细胞中过量产生的酸性钙结合蛋白。22 kDa蛋白(索辛)的水平随着L1210亚系的相对耐药水平而增加。索辛在这些不同亚系中的出现进一步支持了这样一种观点,即这种蛋白的过量产生与多药耐药的普遍现象有关,而不是与特定药物耐药有关,并且对替尼泊苷抗性的选择产生了具有多药耐药性的L1210亚系。