Abstract:

Abstract： Objective To Study effects of the cisplatin-resistance human ovarian cancer SKOV3/DDP cell line on the radiation therapy, and to observe the effect on radiosensitivity and its possible mechanisms by applying MPA on SKOV3/DDP cell line. Methods   MTT assay and the clonogenic assay were used to analyse relative survival rate of cells and radioresistance, with human ovarian cancer cell line SKOV3 and its cisplatin-resistance SKOV3/DDP cell line as research subject exposed to radioactive rays. By the same method to compare relative survival rate and radiosensitivity of SKOV3/DDP cell line treated with non-cytotoxic dose MPA or not. The software Sigma Plot version 10.0 and the multi-target click model S = 1-( 1-eD0/D) n were used to fit cell survival curve，and determining radiation-related parameters to evaluate the sensitizing effect．Flow cytometry was used to detect cell cycle and apoptosis. Results  With the increase of radiation dose, relative survival of SKOV3 and SKOV3/DDP cells was decreased, especially SKOV3 cells. The mean lethal dose (D0) of them were 3.186 and 7.794, and SKOV3/DDP cell line showed stronger radiation resistance with the increase of D0, which indicated that the radiation resistance of SKOV3/DDP cells is stronger than SKOV3 cells. The same methods showed that survival rate of SKOV3/DDP cell treated with the combination of MPA and radiation was lower than that with radiation alone．The average lethal dose (D0) were 4.040 and 7.794，and the sensitivity enhancement ratio (SER) was 1.929. The SKOV3/DDP cells cycle was arrested at phase G0/G1 after treated with MPA combined with radiation，with the proportion of cells at phase S decreased. And the apoptosis rate increased. Conclusion  Human ovarian carcinoma SKOV3/DDP cells have crossed resistance to chemotherapy and radiotherapy；MPA could reverse the resistance of SKOV3/DDP cells to radiation, and its possible mechanism was promoting cell apoptosis and arresting cell cycle process.

Key words: ovarian cancer, medroxyprogesterone acetate;radiosensitivity;apoptosis

摘要：

目的 研究人卵巢癌耐顺铂SKOV3/DDP细胞株对放射治疗的影响，及应用醋酸甲羟孕酮( Medroxyprogesterone Acetate，MPA)于SKOV3/DDP细胞株，探讨其对放射敏感性的影响及其可能机制。方法 以人卵巢癌SKOV3细胞株及其耐顺铂SKOV3/DDP细胞株为研究对象接受不同剂量的放射线照射，采用MTT法、克隆形成实验分析细胞相对存活率及放射抗拒性；应用非细胞毒性剂量MPA联合不同剂量放射线照射于SKOV3/DDP细胞，同法测定联合MPA作用后SKOV3/DDP细胞放射敏感性的变化，采用 Sigma Plot 10.0版软件，利用多靶单击模型S =1-(1-eD0/D)n拟合细胞存活曲线，计算放射相关参数。并采用流式细胞技术 (FCM) 检测细胞周期及凋亡情况。结果 随着放射剂量增大，SKOV3细胞和SKOV3/DDP细胞的相对存活率下降，以SKOV3细胞明显；二者的平均致死剂量(D0)分别为3.186和7.794，D0越大，放射抗拒性越强，表明耐药SKOV3/DDP细胞的放射抗拒性强于SKOV3细胞；同法测定MPA联合放疗组细胞的克隆形成率明显低于单纯放疗组，二者D0分别为4.040、7.794，放射增敏比为1.929。MPA联合放疗作用于SKOV3/DDP细胞，使其细胞周期阻滞于G0/G1期，S期细胞比例下降，并可以增加耐药细胞的凋亡率。结论 人卵巢癌SKOV3/DDP细胞具有放化疗交叉耐受性；MPA可以逆转SKOV3/DDP细胞对放射的抗拒性，其可能机制为促进细胞的凋亡，阻滞细胞周期进程。

关键词: 卵巢肿瘤, 醋酸甲羟孕酮, 放射敏感性, 凋亡