紫草素对卵巢癌细胞株SKOV3放疗敏感性的影响及相关机制研究  

Effects of shikonin on radiosensitivity of human ovarian cancer SKOV-3 cells

作　　者：樊涛[1] 郭彦伟 任金山[1] 苏书娟[1] FAN Tao;GUO Yan-wei;REN Jin-shan;SU Shu-juan(Department of Radiotherapy, The First Affiliated Hospital of Nanyang Medical College, Nanyang 473000 , China;Department of Oncology, The Fifth Affiliated Hospital of Zhengzhou University, Zhengzhou 470000 , China)

机构地区：[1]南阳医学高等专科学校第一附属医院放疗科,河南南阳473000 [2]郑州大学第五附属医院肿瘤科,河南郑州470000

出　　处：《中国病理生理杂志》2019年第4期641-645,共5页Chinese Journal of Pathophysiology

基　　金：河南省教育厅课题(河南省教育厅高等学校重点科研资助项目)(No.18B310025)

摘　　要：目的:研究紫草素对人卵巢癌细胞株SKOV-3的放射增敏作用,并探讨其可能的作用机制。方法:MTT法检测不同浓度(0、5、10、20、40、80和120 mg/L)紫草素对SKOV-3细胞活力的影响;克隆形成实验检测8 mg/L紫草素联合不同剂量(0、2、4、6和8 Gy)X射线照射对SKOV-3细胞增殖能力的影响。将SKOV-3细胞分为4组:对照组、紫草素组(8 mg/L紫草素处理)、8 Gy组(8 Gy X射线照射处理)和紫草素+8 Gy组(给予8 mg/L紫草素处理48 h后,再进行8 Gy X射线照射处理)。PI染色及流式细胞术检测各组SKOV-3细胞周期的变化;Western blot检测各组SKOV-3细胞p-PI3K和p-AKT的蛋白表达水平。结果:在0～80 mg/L浓度范围内,紫草素浓度依赖性抑制SKOV-3细胞活力(P<0.05),IC_(50)为(38.54±0.57) mg/L;紫草素联合放疗处理后的SKOV-3细胞的存活曲线较单独放疗左移,放射增敏比为1.45±0.05。与8 Gy组相比,紫草素+8 Gy组G_2/M期细胞所占比例下降(P<0.05),p-PI3K和p-AKT蛋白水平均显著降低(P<0.05)。结论:紫草素具有提高人卵巢癌细胞株SKOV-3放射敏感性的作用,其作用机制可能与紫草素缓解X射线引起的G_2/M期阻滞及抑制PI3K/AKT信号通路有关。AIM: To investigate the radiosensitizing effect of shikonin on the human ovarian cancer SKOV-3 cells and the underlying mechanism. METHODS: The viability of SKOV-3 cells after treated with shikonin at different concentrations(0, 5, 10, 20, 40, 80 and 120 mg/L) was measured by MTT assay. The proliferation ability of SKOV-3 cells after treated with different doses(0, 2, 4, 6 and 8 Gy) of X-ray radiotherapy was tested by colony formation assay. The SKOV-3 cells were divided into 4 groups: control group, shikonin group(8 mg/L shikonin treatment), 8 Gy group(8 Gy X-ray treatment) and shikonin+8 Gy group(8 mg/L shikonin treatment for 48 h, followed by 8 Gy X-ray treatment). The cell cycle was examined by PI staining and flow cytometry, and the phosphorylation levels of PI3 K and AKT were analyzed by Western blot. RESULTS: In the range of 0~80 mg/L, shikonin decreased the viability of SKOV-3 cells in a concentration-dependent manner(P<0.05). The value of IC50 was(38.54±0.57) mg/L. Compared with radiotherapy alone, the survival curve was markedly shifted to the left after shikonin treatment combined with radiotherapy(P<0.05). The value of radiotherapy sensitization enhancement ratio was 1.45±0.05. Moreover, compared with 8 Gy alone group, the percentage of G2/M phase and the phosphorylation levels of PI3 K and AKT were decreased in shikonin+8 Gy group(P<0.05). CONCLUSION: Shikonin increases the radiosensitivity of SKOV-3 cells, and the mechanism may be related to attenuation of radiation-induced G2/M phase arrest and inhibition of PI3 K/AKT signaling pathway.

关 键 词：紫草素 卵巢癌 放射敏感性 PI3K/AKT信号通路 

分 类 号：R737[医药卫生—肿瘤] R285[医药卫生—临床医学]