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J Korean Cancer Assoc > Volume 27(1); 1995 > Article
Journal of the Korean Cancer Association 1995;27(1): 130-138.
항암제 내성 L1210 변에주들에서 항히스타민제의 내성 극복효과
김재룡, 김성용, 김정희
Reversal Effect of Antihistamines on Multidrug Resistance in Adriamycin - and Vincristine - resistant L1210 Variants
Jae Ryong Kim, Sung Yong Kim, Jeong Hee Kim
ABSTRACT
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 where-by 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 chemasensitizer to overcome the drug resistance, we exam- ined 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 1 uM of astemizole was present, and 8 fold in the presence of 30 uM 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 Ll210VcR was slightly increased in the presence af 1 uM astemizole or 30 uM 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.
Key words: Multidrug resistance, Astemizole, Buclizine, Reversal of resistance
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