Ohkawa K, Tsukada Y, Abe T, Takada K, Hibi N
Dept. of Biochemistry, Jikei University School of Medicine, Tokyo, Japan.
Int J Cancer. 1989 Sep 15;44(3):489-93. doi: 10.1002/ijc.2910440319.
A daunorubicin (DNR)-resistant variant (AH66DR) of alpha-fetoprotein (AFP)-producing rat ascites hepatoma AH66 was established. AH66DR was 169 times more resistant to DNR than AH66. A growth-inhibitory effect due to the decrease in sugar uptake following treatment of the cell lines with specific antibody against highly purified rat AFP was also observed. Pre-incubation of both lines with antibody prior to the measurement of 2-deoxy-D-glucose (2dG) uptake resulted in a 45-55% decrease in 2dG uptake compared to control cells with a 2-fold reduction of Vmax value while the Km remained unchanged. Upon pre-incubating AH66DR with antibody, an increased intracellular level of DNR concentration with reduction of efflux rate was observed. A significantly superior cytotoxic effect against AH66DR, which reached almost the same level as the cytotoxic effect of DNR against AH66, was found, as compared to various other controls when tumor cells were cultured with a mixture of antibody and DNR. Our in vitro results suggest that the DNR-resistance of the AFP-producing tumor cells may be overcome if the cells are treated with specific antibody.
建立了产生甲胎蛋白（AFP）的大鼠腹水肝癌AH66的柔红霉素（DNR）耐药变体（AH66DR）。AH66DR对DNR的耐药性是AH66的169倍。在用针对高度纯化的大鼠AFP的特异性抗体处理细胞系后，还观察到由于糖摄取减少而产生的生长抑制作用。在测量2-脱氧-D-葡萄糖（2dG）摄取之前，用抗体对两个细胞系进行预孵育，与对照细胞相比，2dG摄取减少了45-55%，Vmax值降低了2倍，而Km保持不变。在用抗体预孵育AH66DR后，观察到细胞内DNR浓度增加，外排率降低。当肿瘤细胞与抗体和DNR的混合物一起培养时，与各种其他对照相比，发现对AH66DR具有显著更强的细胞毒性作用，其几乎达到了DNR对AH66的细胞毒性作用水平。我们的体外结果表明，如果用特异性抗体处理细胞，产生AFP的肿瘤细胞的DNR耐药性可能会被克服。
