Intrinsic or acquired antitumordrug resistance in cancer cells is one of the major obstacles in cancer chemotherapy. Especially multidrug resistance(MDR) refers to the phenomenon whereby cells previously exposed to a single drug become resistant,
simultaneously, to a range of structually and functionally unrelated agents. It is very important to overcome the drug-resistance in cancer cells for the success of chemotherapy.
In order to isolate an effective chemosensitizer to overcome the drug resistance, we examined the reversal effects of nine antihistamines on multidrug resistance in an adriamycin-or a vincristine-resistant L1210(L1210AdR or L1210VcR)sublines,
which
show
typical multidrug resistant phenotypes.
The in vitro partial restoration of adriamycin sensitivity in L1210AdR by treatment of nontoxic doses of antihistamines was observed in astemizole, buclizine, megitazine, cetirizine, and terfenadine, in the order of their effectiveness(high to
low). The
sensitivity of L1210AdR to adriamycin was enhanced 13 fold when 1μM of astemizole was present, and 8 fold in the presence of 30μM buclizine. Astemizole and buclizine enhanced also the sensitivity to vinblastine(1160 fold and 933 fold),
dactinomycin(complete reversal and 9 fold). Or vinblastine (30 fold and 5 fold) in L1210AdR. However, the sensitivity to the same drugs in L1210VcR was slightly increased in the presence of 1μM astemizole or 30μM buclizine.
From these results, astemizole or buclizine may be used as a chemosensitizer during cancer chemotherapy. The mechanism by which astemizole or buclizine can reverse the drug resistance in L1210AdR or L1210VcR will be studied.
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