双氢青蒿素联合放疗对肺癌移植瘤裸鼠增敏作用的影响  

The sensitizing effects of combined treatment with dihydroartemisinin and irradiation on human lung cancer in nude mice

作　　者：左占杰 王建东[1] 王松涛[2] 辛永祥[1] 张洪波[1] 

机构地区：[1]武警北京总队医院胸部肿瘤治疗中心,北京100027 [2]武警北京总队医院医疗科,北京100027

出　　处：《现代肿瘤医学》2013年第12期2687-2691,共5页Journal of Modern Oncology

摘　　要：目的:探讨双氢青蒿素(dihydroartemisinin,DHA)对肺癌移植瘤裸鼠的放射增敏作用及对细胞周期和凋亡的影响。方法:体外培养人肺腺癌GLC-82细胞,裸鼠皮下接种GLC-82细胞建立裸鼠移植瘤动物模型,分为空白对照组、单照射组、阳性对照组、DHA(低、中、高)组。经照射后,观察移植瘤鼠肿瘤生长状况,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(enhancement factor,EF)。剥瘤称重,计算抑瘤率。TUNEL法检测各组细胞凋亡指数(apoptosis index,AI)。流式细胞术检测细胞周期和凋亡的变化。结果:实验组裸鼠移植瘤体积明显小于对照组(P<0.05),不同剂量DHA(低、中、高)均能抑制肿瘤生长,并具有较好的放射增敏作用。DHA高剂量联合照射组凋亡指数(AI)为(48.23±6.38)%,与对照组比较差异有统计学意(P<0.01)。DHA可使肺癌GLC-82细胞周期的构成发生明显变化,使S期细胞比例降低,出现明显的G2/M期阻滞,并诱导细胞凋亡。结论:DHA对肺癌GLC-82移植瘤裸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,从而加强射线对肿瘤细胞的杀伤能力。Objective：To investigate the radiosensitization effects, cell cycle and apoptosis of dihydroartemisinin on human lung cancer in nude mice. Methods：Human lung cancer xenografts in nude mice models were established by using of human lung cancer GLC -82 cell lines, which divided into blank control group, radiation alone group, positive control group, dihydroartemisinin （low, medium and high） groups. After irradiated, observed the growth of tumor＇scon- ditions, record epigenetic tumor irradiation time, calculated the delay time of tumor growth and enhancement factor （EF）. After stripped tumor, calculated the inhibition rate. Cell apoptosis index was measured by TUNEL staining. Meanwhile, cell cycle distribution and apoptosis were measured by flow cytometry. Results：The tumor volume of the experiment group was significantly lower than that of the control group （ P 〈 0.05 ）. Dihydroartemisinin （ low, medium and high） groups inhibited the tumor growth better than the blank group, which had the significant radiosensitizing effect. The apoptosis index （AI） of the combination dihydroartemisinin with IR was （48.23 ± 6.38 ） % , and significant difference was found between the two groups （ P 〈 0.01 ）. Cells were treated with dihydroartemisinin which had signif- icant effects on cell cycle, and induced apoptosis, which indicated significant G2/M phase arrest and a decrease in S phase. Condusion：Dihydroartemisinin inhibited the tumor growth, and had the radiosensitizing effects on nude mice. One of the mechanisms maybe that it made significant G2/M phase arrest, and induced apoptosis, so cells were more sensitive to radiation.

关 键 词：双氢青蒿素 肺腺癌 放射增敏 细胞周期 细胞凋亡 

分 类 号：R734.2[医药卫生—肿瘤]