Kasukabe T, Rephaeli A, Honma Y
Department of Chemotherapy, Saitama Cancer Research Institute, Ina, Japan.
Br J Cancer. 1997;75(6):850-4. doi: 10.1038/bjc.1997.151.
A derivative of butyric acid, pivalyloxymethyl butyrate (AN-9), inhibited the proliferation and induced apoptosis of mouse monocytic leukaemia Mm-A cells, although sodium butyrate, but not AN-9, induced differentiation of the cells. AN-9 and DNA-specific antineoplastic agents synergistically inhibited the growth of Mm-A cells, and the simultaneous treatment was required to evoke the maximum growth-inhibitory effect. On the other hand, there was no synergy between butyrate and the drugs, or AN-9 and anti-metabolic agents in inhibiting the growth of the cells, suggesting that the synergistic effect is specific to AN-9 and DNA-reacting agents. AN-9 as a single agent prolonged the survival of mice inoculated with Mm-A cells in a dose-dependent manner. Moreover, administration of AN-9 plus daunorubicin (DNR) markedly prolonged their survival. These results suggest that combination with AN-9 and DNR entails an obvious therapeutic potential.
丁酸衍生物新戊酰氧基甲基丁酸酯（AN-9）可抑制小鼠单核细胞白血病Mm-A细胞的增殖并诱导其凋亡，而丁酸钠虽不能诱导该细胞分化，但能做到这一点。AN-9与DNA特异性抗肿瘤药物协同抑制Mm-A细胞的生长，且需要同时给药才能产生最大的生长抑制效果。另一方面，丁酸盐与这些药物之间，或AN-9与抗代谢药物之间在抑制细胞生长方面不存在协同作用，这表明这种协同效应是AN-9与DNA反应剂所特有的。AN-9作为单一药物能以剂量依赖的方式延长接种Mm-A细胞的小鼠的存活时间。此外，给予AN-9加柔红霉素（DNR）可显著延长它们的存活时间。这些结果表明，AN-9与DNR联合使用具有明显的治疗潜力。
