Chitnis M, Parekh H, Satyamoorthy K
Cellular Chemotherapy Unit, Tata Memorial Centre, Parel, Bombay, India.
Tumori. 1989 Apr 30;75(2):100-5. doi: 10.1177/030089168907500204.
Clofibrate (CPIB), an antihyperlipidemic agent, was utilized as a drug response modulator to modify the cytotoxicity of adriamycin (ADR) in vitro in P388 murine lymphocytic leukemia cells sensitive (P388/S) and resistant (P388/ADR) to ADR. CPIB elicited concentration and time dependent DNA biosynthesis inhibition which was completely reversible up to the concentration of 0.0025% in P388/S. However, only a partial reversibility of DNA biosynthesis inhibition was observed in P388/ADR cells treated with 0.0025% of CPIB. In both P388/S and P388/ADR there was complete and irreversible DNA biosynthesis inhibition at CPIB concentration of 0.005%. These findings were further confirmed by tumorigenicity analysis. CPIB was ineffective in altering ADR cytotoxicity in P388/S cells. However, in P388/ADR, CPIB enhanced ADR cytotoxicity at the lower concentrations of ADR and decreased the cytotoxicity upon increase in ADR concentrations. The enhancement in ADR cytotoxicity by CPIB in P388/ADR was due to increased ADR accumulation which was absent in P388/S cells. The present findings suggest the utility of CPIB as a selective agent to circumvent ADR resistance and to reduce host toxicity due to the drug.
氯贝丁酯（CPIB），一种抗高血脂药物，被用作药物反应调节剂，以在体外改变阿霉素（ADR）对阿霉素敏感（P388/S）和耐药（P388/ADR）的P388小鼠淋巴细胞白血病细胞的细胞毒性。CPIB引起浓度和时间依赖性的DNA生物合成抑制，在P388/S中，高达0.0025%的浓度时，这种抑制是完全可逆的。然而，在用0.0025%的CPIB处理的P388/ADR细胞中，仅观察到DNA生物合成抑制的部分可逆性。在P388/S和P388/ADR中，当CPIB浓度为0.005%时，均存在完全且不可逆的DNA生物合成抑制。这些发现通过致瘤性分析得到进一步证实。CPIB在改变P388/S细胞中的ADR细胞毒性方面无效。然而，在P388/ADR中，CPIB在较低浓度的ADR时增强了ADR的细胞毒性，而在ADR浓度增加时降低了细胞毒性。CPIB在P388/ADR中增强ADR细胞毒性是由于ADR积累增加，而P388/S细胞中不存在这种情况。目前的发现表明CPIB可作为一种选择性药物来规避ADR耐药性并降低药物对宿主的毒性。
