隐丹参酮对肝癌H22荷瘤小鼠放射增敏作用的影响

摘要

背景与目的：醌类化合物可使肿瘤细胞周期发生变化，影响放疗的敏感性。本研究旨在探讨隐丹参酮(cryptotanshinone)对荷H22肝癌小鼠的放射增敏作用及对细胞周期和凋亡的影响。方法：建立小鼠H22肝癌模型，分为空白对照组、单照射(irradiation，IR)组、高浓度隐丹参酮组及低、中、高浓度隐丹参酮联合IR组。经照射后，观察荷瘤鼠肿瘤生长状况，记录肿瘤照射后生长时间，计算肿瘤生长延缓时间和增敏系数。照后22 d处死小鼠，剥瘤称重，计算抑瘤率。流式细胞仪检测细胞周期和凋亡的变化。结果：不同浓度的隐丹参酮联合放疗均能抑制肿瘤生长，并具有较好的放射增敏作用，其增敏比分别为1.22、1.43和2.19。隐丹参酮可使肝癌H22细胞周期的构成发生明显的变化，使S期的细胞比例降低，出现明显的G2/M期阻滞，并诱导细胞凋亡。结论：隐丹参酮对肝癌H22荷瘤小鼠具有较高的抑瘤作用和放射增敏作用。其增敏效应使细胞生长停滞在G2/M期并诱导细胞凋亡，使S期细胞比例降低，从而加强射线对肿瘤细胞的杀伤能力。%Background and purpose:Quinonoids can change the cell cycle distribution of tumor cells, and effect the radiosensitizing. This study aimed to investigate the radiosensitization effects, cell cycle and apoptosis of cryptotanshinone on H22 hepatoma-bearing mice. Methods:The mouse hepatoma H22 model was established, then divided into blank control group, irradiation alone group, high dose of cryptotanshinone group, cryptotanshinone (low, medium and high)+IR groups. After irradiated, observed the growth of tumor’s conditions, record epigenetic tumor irradiation time, calculated the delay time of tumor growth and enhancement factor (EF). After 22 days, mice were killed, stripped tumor, and calculated the inhibition rate. The cell cycle distribution and apoptosis were measured by lfow cytometry. Results:Cryptotanshinone (low, medium and high) groups inhibited the tumor growth better than the blank group, and had the signiifcant radiosensitizing effect. The enhancement factor was 1.22, 1.43,2.19, respectively. Cells were treated with cryptotanshinone which had significant effects on cell cycle, and induced apoptosis, which indicated signiifcant G2/M phase arrest and a decrease in S phase. Conclusion:Cryptotanshinone inhibited the tumor growth and had the radiosensitizing effects on H22 hepatoma-bearing mice. One of the mechanism may be that it might make significant G2/M phase arrest and S phase decreased, and induced apoptosis. So cells were more sensitive to radiation.