三氧化二砷与隐丹参酮不同配比对人肝癌HepG2裸鼠移植瘤的抑制作用

The Effects of Compatibility of Arsenic Trioxide and Cryptotanshinone on Human Hepatocarcinoma Nude Mice

[目的]探讨三氧化二砷(arsenic trioxide,As2O3)与隐丹参酮对人肝癌Hep G2裸鼠的最佳配伍剂量,以期提高As2O3治疗肝癌的临床疗效,并减轻其毒副作用。[方法]建立人肝癌细胞系Hep G2裸鼠肝癌模型,将As2O3(1.25mg·kg-1、2.5mg·kg-1、5.0mg·kg-1)与隐丹参酮(50mg·kg-1,100mg·kg-1,200mg·kg-1)低、中、高三个剂量分为9组联合治疗,计算各组瘤体体积、瘤重及计算肿瘤抑制率;进行血常规及血生化检测。[结果]与模型组比较,除L-L剂量组的平均瘤重外,As2O3与隐丹参酮联合用药组平均瘤重及瘤体积均显著小于模型组(P<0.05)。H-M剂量组瘤体积抑制率和瘤重抑制率分别为(56.38%,54.36%),抑瘤作用大于M-M剂量组(52.25%,45.43%)、L-M剂量组(48.90%,42.13%)、H-L剂量组(50.34%,40.82%)、H-H剂量组(46.10%,35.72%)、M-H剂量组(47.13%,33.68%)、L-H剂量组(32.08%,33.25%)、M-L剂量组(36.38%,31.94%)、L-L剂量组(33.39%,20.71%)。对血常规的影响:与模型组比较,M-H剂量组的白细胞数量显著升高(P<0.05);L-M剂量组、L-H剂量组、M-L剂量组、H-L剂量组、H-M剂量组、H-H剂量组的红细胞数量比模型组有显著下降(P<0.01),M-M剂量组(P<0.05);L-H剂量组、H-M剂量组、H-H剂量组血红蛋白数量有明显下降(P<0.05),M-L剂量组、H-L剂量组的血小板数量下降(P<0.05)。对血生化的影响:除L-L剂量组ALT升高外(P<0.05),As2O3联合隐丹参酮各剂量组ALT含量无统计学意义(P>0.05);L-L剂量组、L-M剂量组的AST含量有显著升高(P<0.05);L-L剂量组、L-H剂量组CREA含量升高(P<0.05);BUN与模型组比较无统计学意义(P>0.05)。[结论]As2O3与隐丹参酮配伍用药可显著的抑制肝癌裸鼠移植瘤的生长,高剂量的As2O3组对血液系统的影响较大,隐丹参酮的联合运用可以起到协同的作用,这为临床上As2O3治疗肝癌疗效的提高提供了一定的参考价值。

[Objective]To study the effects of compatibility of arsenic trioxide and cryptotanshinone on human hepatocarcinoma nude mice. [Methods]Hepatoma cell line（Hep G2 cells） was established,according to the low,middle,high dose of drugs,the experiment was divided into 9 groups（As2O31.25mg·kg^-1, 2.5mg·kg^-1, 5.0mg·kg^-1, CPT 50mg·kg^-1,100mg·kg^-1,200mg·kg^-1）. The size and weight of tumor,inhibition ratio of tumor were calculated,routine blood and blood biochemistry were tested. [Results] As compared with the model group, in addition to the tumor weight of L-L dose group, the tumor weight and volume of combination groups were decreased significantly（ P〈 0.05）. Weight inhibition rate and volume inhibition rate of H-M dose group was 56.38%, 54.36%, and its tumor suppression effect was greater than any other groups, as followings M-M dose group（52.25%, 45.43%）, L-M dose group（48.90%, 42.13%）, H-L dose group（50.34%, 40.82%）, H-H dose group（46.10%, 35.72%）, M-H dose group（47.13%, 33.68%）, L-H dose group（32.08%, 33.25%）, M-L dose group（36.38%, 31.94%）, L-L dose group（33.39%, 20.71%）. Effects on blood routine： compared with model group, the white blood cells of M-H dose group were increased significantly（P〈0.05）, the red blood cells of L-M doses, L-H dose group, M-L dose group, H-L dose group, H-M doses and H-H dose group were significantly decreased（P〈0.01）, the M-M dose group either（P〈0.05）; HGB of the L-H dose group, H-M dose group and H-H dose group were significantly decreased（P〈0.05）, blood platelet of the M-L dose group and H-L dose group were also decreased（ P〈0.05）. Compared with model group, in addition to the L-L dose group（P 〈0.05）, the combination groups of As2O3 and cryptotanshinone had no statistical significance on ALT（P〉0.05）; AST of L-L dose group and L-M dose group were increased significantly（ P〈0.05） while CREA of L-L dose group and L-H dose group were increased（P〈0.05）; BUN of the combination groups had no statistical significance（ P〉 0.05）. [Conclusion] The combination of As2O3 and cryptotanshinone could significantly inhibit the growth of transplantation tumor, high doses of As2O3 groups had bigger influence on blood system, and the combination of cryptotanshinone could improve the effect and decrease toxicity, which provided a certain reference value for As2O3 on clinical treatment of liver cancer.