http://chineseinput.net/에서 pinyin(병음)방식으로 중국어를 변환할 수 있습니다.
변환된 중국어를 복사하여 사용하시면 됩니다.
사람 암세포주 K562 , U937 및 쥐 암세포주 P388 , FM3A 에서의 항암제 다제내성 기전 및 내성극복
도현국(Hyun Kuk Doh),김재석(Jae Seok Kim),손지원(Ji Weon Son),성명식(Myung Sik Sung),김종성(Jong Seong Kim),김선희(Sun Hee Kim),정병선(Byung Sun Jung) 대한내과학회 1992 대한내과학회지 Vol.43 No.3
Background: To study the mechanism of multidrug resistnce (MDR) and overcome MDR in cancer cells, we investigated the combination effects of anticancer agents with calmodulin inhibitors (e,g trifluoroperazine (TFP) and W-7), calcium function modifiers (e.g., quinidine and verapamil) and a protein kinase-C activator (e.g., phorbol ester) in chronic myelogenous leukemic cells, histiocytic lymphoma cells and breast cancer cells. Methods: Some MDR mutant sublines which had cross-resistance to colchicine, actinomycm D, adriamycin and vinblastine were isolated from K562, U937 and FM3A cell lines. MTT analysis was used to measure the level of the cytotoxicity, The cytotoxicity and the combination effects were compared by IC50 (1nhibition concentration50) to control group. Results: In case of U937/MDR, TFP increased the combination effect to tenfold in colchicine (COL), eightfold in vinblastine (VLB) and thirteenfold in actinomycin D (ACT-D). Quinidine increased the effect to threefold in COL, fourfold in VLB and sevenfold in ACT-D. Verapamil also increased the effect to sevenfold in COL, sixfold in VLB fivefold in ACT-D. In case of K562/MDR, TFP, quinidine and verapamil each increased the combination effect to sixfold, twelvefold and thirteenfold in COL and sixfold, fivefold and fivefold in adriamycin (ADM). W-7 in concentration of 20uM increased the combination effect to six point sevenfold in ACT-D, twofold in COL and two point threefold in ADM. In the combination of COL with 0.48uM TPA, the cytotoxicity was reduced to two point eightfold in case of FM3A/MDR. TPA (12-0-tetradecanoyl phorbol 13-acetate), in concentration of 0.48uM, a phorbol ester, reduced the cytotoxicity to two point eightfold in case of FM3A/ MDR. Conclusion: When the combination effects of anticancer agents with calmodulin inhibitors (e.g TFP and W -7) and calcium function modifiers (e.g., quinidine and verapamil) were examined, the cytotoxicity changes of anticancer agents were small in drug sensitive cells. But in MDR cells, the combination effects were prominent. The reduced cytotoxicity of anticancer agents by TPA suggested that protein kinase-C might be related with the mechanism of acquiring drug resistance on cancer cells.