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卵巢癌类器官模型的建立及在药物敏感性测试中的应用

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目的 使用临床样本成功构建卵巢癌类器官模型,选用卵巢癌临床常用一线化疗药物卡铂,探究不同处理因素对卵巢癌类器官药物敏感性测试结果的影响,为肿瘤患者个体化用药和精准治疗方案的选择提供依据。方法 采用不同细胞密度、不同药物剂量、不同药物作用时间对 2 例卵巢癌类器官OC-1、OC-2 进行处理,设置对照组和处理组,比较分析 2 例卵巢癌类器官对卡铂的敏感性。药物剂量上设计 6 组不同浓度(100、50、10、1、0。1、0。01 μmol/L)卡铂作用于 2 例卵巢癌类器官。药物作用时间上,以相同剂量 100 μmol/L卡铂分别作用于 2 例卵巢癌类器官 3~9 d。细胞药物敏感性测试上通过CCK-8 法检测细胞增殖活力,根据肿瘤细胞相对抑制率(T/C)比较分析不同处理因素对卵巢癌类器官药物敏感性测试结果的影响。结果 ①在细胞密度的选择上,每孔接种 8 000 个和 4 000 个细胞时,50~100 μmol/L卡铂均对卵巢癌类器官OC-1、OC-2 的生长抑制作用显著(P<0。05),两者的抑制作用差异无统计学意义(P>0。05)。②在不同药物剂量的选择上,50~100 μmol/L卡铂均对卵巢癌类器官OC-1、OC-2 体外有效(T/C≤50%),而其余 4 个剂量组体外无效。③在药物作用时间的选择上,100 μmol/L的卡铂对类器官OC-1、OC-2 在 3~9 d观测期中,与对照组相比,随时间延长具有更显著的生长抑制作用(P<0。01 或P<0。001)。结论 通过卵巢癌类器官模拟体内真实的肿瘤环境下,化疗药物卡铂在不同剂量、不同作用时间下均影响卵巢癌药物敏感性检测结果。利用卵巢癌类器官为卵巢癌患者设计个体化用药方案具有十分积极的意义。
Establishment of the organoids for ovarian cancer and its application in drug sensitivity test
Objective To successfully construct ovarian cancer organoid models by using clinical samples,select the commonly used first-line drug carboplatin in ovarian cancer clinical practice,explore the impact of different treatment factors on the drug sensitivity test results of ovarian cancer organoid,and provide a basis for personalized medication and precise treatment plan selection for tumor patients.Methods Two cases of ovarian cancer organoids OC-1 and OC-2 were treated with different cell densities,drug doses,and drug action times.Control and treatment groups were set up to compare and analyze the sensitivity of the two cases of ovarian cancer organoids to carboplatin.In terms of drug doses,six different concentrations of carboplatin(drug doses of 100,50,10,1,0.1,0.01 μmol/L)were designed to apply in the two cases of ovarian cancer organoids.In terms of drug action time,at the same dose of 100 μmol/L carboplatin acted on two cases of ovarian cancer organoids for 3~9 days.In the cell drug sensitivity test,CCK-8 method was used to detect cell proliferation activity,and the impact of different treatment factors on the drug sensitivity test results of ovarian cancer organoids was compared and analyzed based on the relative inhibition rate(T/C)of tumor cells.Results ①In the selection of cell density,when inoculating 8 000 and 4 000 cells/well,50~100 μmol/L carboplatin had a significant inhibitory effect on the growth of ovarian cancer organoids OC-1 and OC-2(P<0.05),and there was no statistically significant difference in their inhibitory effects(P>0.05).②In the selection of different drug doses,50~100 μmol/L carboplatin was effective in vitro for ovarian cancer organoids OC-1 and OC-2(T/C≤50%),while the other fore dose groups were ineffective in vitro.③In the selection of drug action time,100 μmol/L carboplatin showed a more significant growth inhibitory effect on organoids OC-1 and OC-2 over a 3~9 day observation period(P<0.01 or P<0.001).Conclusion By simulating the real tumor environment in vivo through ovarian cancer organoids,the chemotherapy drug carboplatin affects the drug sensitivity test results of ovarian cancer drugs at different doses and action times.The use of ovarian cancer organoids to design personalized medication plans for ovarian cancer patients has a very positive significance.

Ovarian cancerOrganoidCarboplatinDrug sensitivity

尹秀英、欧阳小芬、庄婷娟、陈丽萍、柯玉秀、袁贤琳

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武警广东省总队医院妇产科,广州 510507

广州市番禺区中医院,广州 511408

广州开发区医院,广州 510730

广东轻工职业技术学院生命健康技术学院,广州 510300

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卵巢癌 类器官 卡铂 药物敏感性

2021年度广东省医学科研基金项目

B2021288

2024

中国处方药
南方医药经济研究所

中国处方药

影响因子:0.649
ISSN:1671-945X
年,卷(期):2024.22(8)