[Cross-resistance to anticancer drugs in acute myeloblastic leukemia Pgp expressing K562 cell line]

ABSTRACT

Drug resistance remains one of the most important clinical obstacles in the treatment of some cancers. This drug resistance referred to as Multidrug Resistance [MDR] induces cross-resistance to many chemotherapy agents such as anthracyclines, vinca alkaloides, epipodophyllotoxins and Taxol. MDR is most likely due to the reduction of drug accumulation with an energy-dependent drug efflux pump. This drug pump is a 170 kDa transmembrane glycoprotein [Pgp]. We developed a resistance subline of K562 by stepwise increase in concentration of Doxorubicin, and Pgp expression was verified by flowcytometry and RT-PCR methods. Cross resistance of the resistant cell line to Etoposide, Vincristine and Taxol was analyzed by MTT assay. IC[50] [the level of drug concentration inhibiting 50% of cell growth] of Doxorubicin, Etoposide and Taxol of parental K562 came out to be 100ng/ml and it was 50 ng/ml for vincristine. IC[50] levels of these drugs on resistant K562 were 500, 500, 450 and 450ng/ml. These drugs also displayed 5-, 5-, 4.5-, and 9- fold resistance respectively. According to the results, expression of Pgp confers MDR phenotype to the K562 cell line and makes it resistant to most of anticancer drugs including anthracyclines, vinca alkaloides, epipodophyllotoxins and taxans. This MDR phenotype is a major obstacle of cancer treatment and in recent years investigators are trying to reverse it by gene therapy