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Benzotriazepin 유도체의 암세포에 대한 다약제내성 억제효과
김미혜(Mi Hye Kim),최상운(Sang Un Choi),최은정(Eun Jung Choi),김성수(Sung Soo Kim),최중권(Jung Kwon Choi),안진희(Jin Hee Ahn),이정옥(Chong Ock Lee),권광일(Kwang ll Kwon) 대한약학회 2005 약학회지 Vol.49 No.1
The occurrence of resistance to chemotherapeutic drugs is a major problem for successful cancer treatment. This resistant phenotype of cancer cell frequently reveals a broad spectrum to structurally and/or functionally unrelated anti-cancer drugs, termed multidrug resistance (MDR). Overexpression of P-glycoprotein (P-gp), a transmembrane drug efflux pump, is a major mechanism of MDR. Accordingly, considerable effort has been directed towards to development of compounds that inhibit P-gp, reverse the MDR phenotype and sensitize cancer cells to conventional chemotherapy without undesired toxicological effects. In an effort to search for novel MDR reversal agent, we tested the cytotoxicity of paclitaxel, a well-known substrate of P-gp, against P-gp-expressing HCT15 and HCT15/CL02 human colorectal cancer cells in the presence or absence of benzotriazepin analogues, as well as against P-gp-negative A549 human non-small cell lung and SK-OV-3 human ovarian cancer cells in vitro. Among the compounds tested, the agents that have phenyl amide moiety at 3 position remarkably increased the cytotoxicity of paclitaxel against P-gp-expressing cancer cells, but not against P-gp-negative cancer cells. BTZ-15 and BTZ-16 at 4μM revealed similar MDR reversal activity to 10μM verapamil, a well-known MDR reversal agent.
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