P-glycoprotein expression and schedule dependence of adriamycin cytotoxicity in human colon carcinoma cell lines

摘要: Abstract Four human colon cancer cell lines (SW620, LS 180, DLD-I, and HCT-15) Adriamycin-resistant sub-lines with varying degrees of P-glycoprotein expression were studied to evaluate the reversibility Adriamycin resistance in cancer. Two groups studied. In first, including a series SW620 DLD-I sub-lines, parental HCT-15 cells, has major role resistance, as evidenced by correlation between multidrug-resistance gene mdr-I its product, (Pgp), decreased drug accumulation verapamil. these lines, increasing doses verapamil are required fully reverse levels resistance. second group, SW620, 180 cells Adriamycin-selected does not have There was schedule dependence cytotoxicity modulating which determinant exposure (defined product concentration time treatment) needed achieve given percent kill reduced much 9-fold when treated for 7 days compared 3 hr. By comparison, played lesser role, necessary increased under conditions continuous treatment. some carcinoma Pgp appears play significant Adriamycin, this can be overcome use competitive inhibitors Pgp. The sensitivity treatment observed P-glycoprotein-mediated suggests that administration drugs infusion may valuable reversing clinical mediated predominantly P-glycoprotein.