三氧化二砷联合丹参酮胶囊抗肝癌的作用效果与机制研究
Effect and mechanism of Arsenic trioxide combined with tanshinone capsule on liver cancer xenograft in nude mice
目的 考察三氧化二砷(Arsenic trioxide,As2O3)联合丹参酮胶囊对肝癌裸鼠移植瘤的作用效果与机制。方法 建立裸鼠人肝癌移植瘤模型,通过19 d不同的药物干预,比较各组裸鼠的肿瘤生长曲线和瘤重;采集血液进行血常规和生化常规分析;原位末端标记法(TUNEL)检测瘤体组织凋亡情况;免疫组织化学和western blot 检测凋亡相关蛋白的表达。结果 生长曲线和瘤重等数据显示随着给药时间的延长,As2O3 低剂量组、As2O3 阳性对照组、丹参酮胶囊组以及As2O3 低剂量联合丹参酮胶囊组均能表现出一定的抑瘤效果,且与As2O3 低剂量组和丹参酮胶囊组相比,联合组的抑瘤效果更明显(p<0.01)。丹参酮胶囊对裸鼠血象几乎引起没有明显的变化,As2O3两个剂量组都可以显著的降低白细胞、红细胞的含量,升高血小板的含量(p<0.05或p<0.01)。As2O3 低剂量联合丹参酮胶囊则可以逆转这种趋势,甚至可以使各检测指标恢复到正常的水平。As2O3 低剂量联合丹参酮胶囊组比As2O3 低剂量组或丹参酮胶囊组促肝癌细胞凋亡率显著上调(p<0.01)。As2O3低剂量联合丹参酮胶囊能够下调抗凋亡蛋白XIAP的表达(p<0.01),上调促凋亡蛋白Bax、PARP的表达(p<0.01)。结论 低剂量As2O3 联合丹参酮胶囊具有协同增效、减毒抗肝癌的作用,诱导肝癌细胞凋亡并减低血象毒性是其作用机制之一。
Objective To elucidate the effect of Arsenic trioxide (As2O3) combined with tanshinone capsule on liver cancer xenograft in nude mice and to investigate the possible mechanism. Methods Liver cancer xenograft model was established in nude mice. After the 19 days of different drug intervention, tumor growth curve was drawn and tumor weight between groups were comparied; Collected blood was analysised on blood routine and biochemical routine; TdT-mediated dUTP nick end labeling(TUNEL) detected tissue apoptosis of tumors;The expression of apoptosis related proteins were detected by immunohistochemistry and western blot. Results Growth curve and tumor weight data showed that, with the extension of delivery time, such as As2O3 low dose group, As2O3 positive control group, tanshinone capsule group and combination group could show some tumor suppression effect.Compared with As2O3 low-dose group and tanshinone capsule group, the tumor suppression effect of combination group was more obvious(p<0.01). Tanshinone capsule almost caused no obvious change on nude mice blood. However, As2O3 both dose groups could significantly reduce the white blood cells and red blood cells and increase the content of platelet (p < 0.05 or p <0.01). However the combination group could reverse this trend, even could make the detection index return to normal levels. The apoptosis rate of combination group increase significantly than As2O3 low-dose group and tanshinone capsule group(p<0.01). The combination group could cut the expression of antiapoptotic protein XIAP(p<0.01)and promote the expression of apoptosis proteinPARP and Bax(p<0.01). Conclusion Low-dose As2O3 combined tanshinone capsule has the attenuated synergies effect in the resistance to liver cancer. Inducing liver cancer cell apoptosis and reducing the toxicity to blood is one of its mechanisms.
张广顺、楼招欢、廖广辉、张光霁、申力
肿瘤学药学基础医学
s2O3丹参酮胶囊肝癌增效减毒
arsenic trioxidetanshinone capsuleliver cancerEnhance the effectiveness and reduce toxicity
张广顺,楼招欢,廖广辉,张光霁,申力.三氧化二砷联合丹参酮胶囊抗肝癌的作用效果与机制研究[EB/OL].(2016-06-01)[2025-07-16].http://www.paper.edu.cn/releasepaper/content/201606-88.点此复制
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