ENHANCED POTENCY OF DAUNORUBICIN AGAINST MULTIDRUG-RESISTANT SUBLINE KB-CH(R)-8-5-11 BY A PULSED MAGNETIC-FIELD

Tumor cell resistance to many unrelated anticancer drugs is a major ob stacle during cancer chemotherapy. One mechanism of drug resistance is thought to be due to the efflux of anticancer drugs caused by P-glyco protein. In recent years, magnetic fields have been found to enhance t he potency of anticancer drugs, with favorable modulation of cancer th erapy. In this study, KB-Ch(R)-8-5-11, a multidrug resistant (MDR) hum an carcinoma subline, was used as a model to evaluate the ability of p ulsed magnetic fields (PMF) to modulate the potency of daunorubicin (D NR) in vivo and to determine the appropriate order of exposure to drug s and PMF using an in vitro cytotoxicity assay. Solenoid coils with a ramped pulse current source were used at 250 pulses per second for bot h in vivo and in vitro experiments. For the in vivo study, KB-Ch(R)-8- 5-11 cells were inoculated into thymic Balbc-nu/nu female mice. Treatm ent was begun when the average tumor volume reached 250-450mm(3). Trea tment consisted of whole body exposure to PMF for one hour, followed i mmediately by intravenous (iv) injection of 8mg/kg DNR designated as d ay 0, and repeated on days 7 and 14. Among the various groups, signifi cant differences in the tumor volume were found between PMF+saline and PMF+DNR groups (p=0.0107) at 39 days and 42 days (p=0.0101). No mice died in the PMF alone group, and no toxicity attributable to PMF was f ound during the experimental period. For the in vitro studies, the sul forhodamine blue (SRB) cytotoxicity assay was used to determine the ef fect of the sequence which cells are exposed to PMF and/or DNR. Cells were exposed to PMF either before (pre-PMF) or after (post-PMF) drug w as added. Results showed that the IC50 was significantly different bet ween controls and pre-PMF + DNR groups (P=0.0096, P=0.0088). The IC50 of the post-PMF + DNR group was not found to be significantly differen t from control groups. Thus, the data in this report demonstrates that PMF enhanced the potency of DNR against KB-Ch(R)-8-5-11 xenograft in vivo, while the efficacy of DNR was potentiated in vitro by PMF exposu re only when PMF exposure occurred in the presence of drug. The data i n vitro suggest that the mechanism by which PMFs modulate DNR's potenc y may be by inhibition of the efflux pump, P-glycoprotein. Further wor k to determine conditions for maximum modulation of drug potency by PM Fs is warranted.