阿帕替尼联合氟唑帕利对人卵巢癌顺铂耐药细胞增殖能力的影响  

Effect of apatinib combined with fluzoparib on proliferation ability of human ovarian cancer cisplatin-resistant cells

作　　者：杨颖慧 高磊 赵宏伟[2] Yang Yinghui;Gao Lei;Zhao Hongwei(Second Clinical Medical College,Shanxi Medical University,Taiyuan 030001,China;Department of Gynecology Oncology,Shanxi Province Cancer Hospital,Shanxi Hospital Affiliated to Cancer Hospital,Chinese Academy of Medical Sciences,Cancer Hospital Affiliated to Shanxi Medical University,Taiyuan 030013,China)

机构地区：[1]山西医科大学第二临床医学院,太原030001 [2]山西省肿瘤医院、中国医学科学院肿瘤医院山西医院山西医科大学附属肿瘤医院妇瘤科,太原030013

出　　处：《肿瘤研究与临床》2023年第7期494-499,共6页Cancer Research and Clinic

基　　金：山西省重点研发计划(201903D321174);北京市希思科临床肿瘤学研究基金(Y-HR2018-330)。

摘　　要：目的探讨阿帕替尼及氟唑帕利对人卵巢癌顺铂耐药细胞增殖能力的影响。方法选择人卵巢癌细胞株SKOV3和人卵巢癌顺铂耐药细胞株SKOV3/DDP。使用不同浓度顺铂(1、2、4、8、16、32、64、128 μg/ml)处理SKOV3、SKOV3/DDP细胞不同时间, CCK-8法检测SKOV3、SKOV3/DDP细胞增殖率及半数抑制浓度(IC50), 并计算SKOV3/DDP细胞的耐药倍数。使用不同浓度阿帕替尼(4、8、16、32、64 μmol/L)、氟唑帕利(148.15、222.22、333.33、500.00、750.00 μmol/L)分别处理SKOV3/DDP细胞24、48、72 h, 采用CCK-8法检测细胞增殖率并计算IC50。将SKOV3/DDP细胞分为空白对照组(未进行药物处理的细胞)、顺铂组、顺铂+阿帕替尼组、顺铂+氟唑帕利组、顺铂+氟唑帕利+阿帕替尼组, 分别给予相应药物干预, CCK-8法检测每组细胞的增殖率。结果相同浓度顺铂作用相同时间, SKOV3细胞增殖率均低于SKOV3/DDP细胞, 差异均有统计学意义(均P<0.05)。4、8、16、32、64 μmol/L阿帕替尼作用于SKOV3/DDP细胞24 h时IC50为742.1 μmol/L, 48 h为156.8 μmol/L, 72 h为77.5 μmol/L;与对照组比较, 有效浓度大于32 μmol/L的阿帕替尼作用SKOV3/DDP细胞的细胞增殖率明显降低, 差异均有统计学意义(均P<0.05)。148.15、222.22、333.33、500.00、750.00 μmol/L氟唑帕利作用于SKOV3/DDP细胞24 hIC50为878.5 μmol/L, 48 h为406.7 μmol/L, 72 h为283.3 μmol/L;氟唑帕利作用24 h时, 药物有效浓度≥333.33 μmol/L后SKOV3/DDP细胞的细胞增殖率降低, 与对照组比较差异均有统计学意义(均P<0.05);作用48 h和72 h时, 药物有效浓度≥148.15 μmol/L后SKOV3/DDP细胞的细胞增殖率降低, 与对照组比较差异均有统计学意义(均P<0.05);顺铂5 μg/ml+阿帕替尼64 μmol/L组较顺铂5 μg/ml组细胞增殖率降低[(40.4±1.4)%比(62.7±1.4)%, t=20.22, P<0.001];顺铂5 μg/ml+氟唑帕利290 μmol/L组较顺铂5 μg/ml组细胞增殖率降低[(5.2±0.4)%比(62.7±1.4)%, t=52.04, P<0.001];顺铂5 μg/ml+Objective To investigate the effect of apatinib and fluzoparib on the proliferation ability of cisplatin-resistant human ovarian cancer cells.Methods Human ovarian cancer cells SKOV3 and cisplatin-resistant SKOV3/DDP cells of human ovarian cancer were treated with different concentrations of 1,2,4,8,16,32,64,128µg/ml cisplatin at different times;CCK-8 method was used to detect the proliferation rate and half-inhibitory concentration(IC50)of SKOV3 and SKOV3/DDP cells,and the drug-resistance fold of SKOV3/DDP cell was also calculated.SKOV3/DDP cells were treated with different concentrations of apatinib(4,8,16,32,64μmol/L)and fluzoparib(148.15,222.22,333.33,500.00,750.00μmol/L)for 24 h,48 h and 72 h,respectively;the cell proliferation rate was determined by using CCK-8 method and IC50 was calculated.SKOV3/DDP cells were divided into the blank control group(cells untreated with drugs),cisplatin group,cisplatin+apatinib group,cisplatin+fluzoparib group,cisplatin+fluzoparib+apatinib group,and drug intervention was given in each group;the inhibition rate of cells in each group was detected by using CCK8 method.Results The proliferation rate of SKOV3 cells treated with the same concentration of cisplatin for the same time was lower than that of SKOV3/DDP cells,and the differences were statistically significant(all P<0.05).The IC50 of SKOV3/DDP cells treated with 4,8,16,32,64μmol/L apatinib was 742.1μmol/L at 24 h,156.8μmol/L at 48 h,and 77.5μmol/L at 72 h.Compared with the control group,the proliferation rate of SKOV3/DDP cells treated with apatinib at an effective concentration greater than 32μmol/L was significantly decreased,and the differences were statistically significant(all P<0.05).The IC50 of SKOV3/DDP cells treated with 148.15,222.22,333.33,500.00,750.00μmol/L fluzoparib was 878.5μmol/L at 24 h,406.7μmol/L at 48 h,and 283.3μmol/L at 72 h.When the effective concentration of fluzoparib was more than 333.33μmol/L for 24 h,the proliferation rate of SKOV3/DDP cells was lower than that of the control gr

关 键 词：卵巢肿瘤 耐药性 阿帕替尼 氟唑帕利 

分 类 号：R737.31[医药卫生—肿瘤]