ENHANCEMENT OF SENSITIVITY TO ADRIAMYCIN IN RESISTANT P388-LEUKEMIA BY THE CALMODULIN INHIBITOR TRIFLUOPERAZINE

  • 1 January 1983
    • journal article
    • research article
    • Vol. 43  (8) , 3696-3699
Abstract
Resistance to the cytotoxic effects of daunomycin and adriamycin (ADR) in sublines of Ehrlich ascites and P388 mouse tumors has been demonstrated to be due to reduced cellular accumulation and retention of drug. Here, the effect of the calmodulin inhibitor trifluoperazine on the cellular accumulation, retention and cytotoxic effects of ADR in ADR-sensitive (P388/S) and ADR-resistant (P388/R) P388 mouse leukemia cells was determined. In cells treated in suspension culture for 24 h or for 1 h followed by plating in soft agar, a noncytotoxic concentration of 4 .mu.M trifluoperazine enhanced the sensitivity to ADR 2- to 6-fold in P388/R, but not in P388/S, cells. A marked enhancement in cellular retention rather than accumulation of ADR in only P388/R cells was obtained with trifluoperazine treatment. The possible novel use of phenothiazines to improve drug sensitivity of tumors resistant to ADR treatment is suggested.