活性氧对卵巢癌细胞COC1及COC1/DDP的化疗敏感性分析  

The Chemotherapy Sensitivity Analysis of the Impact of Reactive Oxygen Species on Ovarian Cancer Cells COC1 and COC1 /DDP

作　　者：马骏[1] 杨洁[2] 沈浩然[1] 王诚洁 王育[1] 

机构地区：[1]上海交通大学医学院附属仁济医院,上海200127 [2]上海交通大学医学院,上海200025

出　　处：《实用妇产科杂志》2014年第7期535-540,共6页Journal of Practical Obstetrics and Gynecology

基　　金：上海市科委科研项目(编号:11ZR1421900)

摘　　要：目的:比较卵巢癌顺铂(DDP)敏感株COC1及耐药株COC1/DDP细胞组织层面活性氧(ROS)水平,探讨ROS水平与卵巢肿瘤化疗敏感性的关系。方法:应用流式细胞法检测两株细胞ROS水平及在使用ROS生成剂大黄素(Emo)50μmol/L、清除剂N-乙酰-L-半胱氨酸(NAC)10 mmol/L、DDP 10μg/ml不同时间及干预手段后ROS的变化;采用MTS法检测细胞在用DDP、DDP+Emo、DDP+Emo+NAC干预24小时后细胞增殖活力的变化;应用冰冻切片荧光染色法检测COC1及COC1/DDP细胞成瘤后组织层面ROS水平。结果:1COC1的ROS水平绝对值明显高于COC1/DDP(P<0.05);2使用NAC后,COC1及COC1/DDP细胞分别与对照组比较,其相对ROS水平明显下降(P<0.05),而使用Emo后,相对ROS水平增加(P<0.01),但两组组间比较,差异无统计学意义(P>0.05)。3DDP单独处理后,COC1及COC1/DDP的ROS水平在24小时显著上升,分别与其1、2、4、6小时时比较,差异均有统计学意义(P<0.05),但两组在不同时间段的组间比较,差异均无统计学意义(P>0.05)。4DDP联用Emo后,两株细胞ROS呈时间依赖性增长,在24小时时变化显著,且COC1细胞的反应性高于COC1/DDP(P<0.05)。5COC1及COC1/DDP在单药DDP(<5μg/ml)的作用下,细胞的相对生存率呈剂量依赖性变化;在联用Emo后,细胞相对生存率明显下降;而在加用NAC后略有上升。6组织层面的ROS水平COC1比COC1/DDP高2.21倍(P<0.05)。结论:COC1比COC1/DDP在细胞及组织层面ROS水平有明显增高,采用Emo和NAC干预ROS水平后,对于化疗敏感性发生变化,提升ROS水平对其化疗敏感性增强。Objective.To compare the reactive oxygen species （ROS）levels of cisplatin-sensitive ovarian tumor cell strain COC1 and cisplatin-resistant ovarian tumor cell strain COC1/DDP in terms of cell and tissue and to explore the correlation between ROS levels and chemosensitivity of ovarian cancer. Methods： Flow cytometry was applied to examine the ROS levels of COC1 and COC1/DDP with the use of Emo 50 pmoVL, NAC 10 mmol/L and DDP 10 μg/ml at different times and the changes of ROS levels after intervention. MTS assay was used to analyze the change of the proliferation of the two Cell strains after 24 hours＇ intervention of DDP, DDP ＋ Emo and DDP ＋ Emo ＋ NAC. Fluorescent staining of frozen sections was applied to examine the ROS levels of COC1 and COC1/DDP after xenograft in terms of tissue. Results：①The absolute value of the ROS level of COCl was significantly higher than that of COC1/DDP （P 〈 0. 05）. ②When compared to con- trol group,the relative ROS levels in COC1 and COC1/DDP cells both significantly decreased（ P 〈0. 05）af- ter using the ROS scavenger NAC, while the relative ROS levels in COC1 and COC1/DDP cells both in- creased （P 〈 0.01 ）after using the ROS generating agent Emo, however,when compared between COC1 and COC1/DDP ceils,the difference was not statistically significant（ P 〉 0. 05）. ③After reatment with DDP alone, the ROS levels of COC1 and COC1/DDP cells increased significantly after 24 hours, when compared with those after 1,2,4 and 6 hours respectively（P〈0.05）. But when compared between the two groups at differ- ent times respectively, the difference was not statistically significant （P 〉 0.05 ）. ④After the treatment with DDP and Emo,the two cell strains showed a time-dependent increase in ROS levels. The change was signifi- cant after 24 hours, and reactivity to drugs of COC1 cells was higher than that of COC1/DDP cells（ P 〈 0.05）. ⑤After the treatment of DDP alone （ 〈 5 μg/ml）, the relative growth rate of cells showed dose-de-

关 键 词：卵巢肿瘤 活性氧 顺铂 

分 类 号：R737.31[医药卫生—肿瘤]