盐酸吡哆醇与化疗药物联用对小鼠肝癌细胞H22的抑制作用

Inhibitory effect of pyridoxine hydrochioride combined with chemotherapeutics on mice hepatoma cellline H22

目的探讨盐酸吡哆醇（PN）单用及与常用化疗药物联用对体外培养小鼠肝癌细胞H22的作用。方法以四甲基偶氮唑盐（Mrr）法测定PN及10种抗肿瘤药物单用及联用对H22细胞增殖的影响，应用免疫细胞化学法检测PN作用前后H22细胞内PN的分布及细胞形态学变化。结果经与5mmol／LPN培养24h后，H22细胞体积明显增大，为对照组的1．48倍，细胞核呈碎片状，PN活性形式磷酸吡哆醛（PLP）浓集于细胞质；PN与多柔比星合用抑制率（IR）为0．63，低于多柔比星单用的0．71（P〈0．01），且药物联用指数（CI）〈0．9，提示二者联用相互拮抗；PN与异环磷酰胺合用IR为0．60，高于异环磷酰胺单用的0．40（P〈0．05），且CI〉0．9，提示二者联用有相加作用。结论PN处理可增加H22细胞内PLP含量，导致肿瘤细胞体积增大，细胞核碎裂并使细胞增殖受抑制；与多柔比星合用有拮抗作用，需注意避免；而与异环磷酰胺合用有相加作用，有助于发挥药效和减轻不良反应。

Objective To observe the inhibitory effect of pyridoxine hydrochloride （PN） combined with common chemotherapeutics on mice hepatoma cells H22 in vitro. Methods MTF assay was used to determine the effects of PN in combination with 10 different antineoplastic agents on H22 ceils, and immuno- histochemistry was used to observe the distribution of PN in H22 cells and morphologic changes of the cells before and after PN treatment. Results After 24 hours incubation with 5 mmol/L PN, the treated cells expanded apparently with nucleus chipping. PN entered the tumor cell and was mainly condensed in cytoplasma and H22 cells were sensitive to PN. When administered concomitantly with chemotherapic agents, most of the combinations showed antagonistic effects while a few of the combinations were additive. For instance, doxorubicin （ADM） used in combination with PN inhibited cell proliferation with an IR value （IR = 0.63） much lower than ADM alone （IR = 0.71, P〈 0.01）, and the CI value was less than 0.9, which indicated an antagonistic effect. However, PN in combination with ifosfamide （ICTX） showed additive effect （CI 〉 0.9）, and the IR value （IR = 0.60） in combined group was higher than that （IR = 0.40） in ICTX group （P 〈 0.05）. Conclusion PN treatment could increase the intracellular PLP level and result in growth inhibition and cell death, and combined administration of PN and ICTX might be a potential method to improve efficacy and to reduce toxic effects while a co-administration of PN and ADM should be avoided.