TAS-102联合奥沙利铂对肝细胞癌SNU-449细胞增殖、迁移和侵袭以及凋亡的影响  

Effects of TAS-102 combined with oxaliplatin on proliferation,migration,invasion and apoptosis of hepatocellular carcinoma SNU-449 cells

作　　者：刘杨[1] 陶璐 李玉梅[1] 陈宇佛 汪蕊[1] LIU Yang;TAO Lu;LI Yu-mei;CHEN Yu-fo;WANG Rui(Department of Medical Oncology,the First Affiliated Hospitalof Bengbu Medical College,Bengbu 233004,Anhui Province,China)

机构地区：[1]蚌埠医学院第一附属医院肿瘤内科,安徽蚌埠233004

出　　处：《中国临床药理学杂志》2024年第9期1262-1266,共5页The Chinese Journal of Clinical Pharmacology

基　　金：安徽省自然科学基金资助项目(2208085MH246);蚌埠医学院自然科学基金资助项目(2020byzd076)。

摘　　要：目的探究曲氟尿苷替匹嘧啶片(TAS-102)联合奥沙利铂(L-OHP)对肝细胞癌SNU-449细胞增殖、迁移、侵袭和凋亡的影响及其可能机制。方法将SNU-449细胞分为对照组(正常培养)、TAS-102组(2μg·mL^(-1)TAS-102)、奥沙利铂组(1.2μg·mL^(-1)L-OHP)以及联合组(2μg·mL^(-1)TAS-102+1.2μg·mL^(-1)L-OHP)。以细胞计数盒8法检测细胞的增殖能力;以Transwell实验检测细胞迁移和侵袭能力;以流式细胞术分析细胞的凋亡率;以蛋白质印迹法检测细胞中B淋巴细胞瘤-2(Bcl-2)、Bcl-2相关X蛋白(Bax)、E-钙黏蛋白(E-cadherin)和波形蛋白(Vimentin)的蛋白表达水平。结果对照组、TAS-102组、奥沙利铂组和联合组细胞的存活率分别为(100.00±2.98)%、(80.26±5.55)%、(78.49±5.76)%和(47.82±4.26)%,细胞迁移数量分别为436.83±27.50、228.17±15.87、171.67±19.49和113.83±11.34,细胞侵袭数量分别为332.67±19.95、205.33±13.65、219.67±14.49和116.83±11.30,凋亡率分别为(2.32±0.07)%、(6.74±0.24)%、(6.37±0.18)%和(10.67±0.41)%,Bax蛋白相对表达水平分别为0.28±0.01、0.53±0.03、0.75±0.03和1.11±0.03,Bcl-2蛋白相对表达水平分别为0.65±0.03、0.32±0.02、0.23±0.02和0.13±0.01,E-cadherin蛋白相对表达水平分别为0.15±0.01、0.24±0.02、0.35±0.02和0.64±0.02,Vimentin蛋白相对表达水平分别为0.65±0.03、0.27±0.01、0.34±0.02和0.18±0.01。各给药组与对照组比较,联合组与单药组比较,以上指标在统计学上差异均有统计学意义(均P<0.05)。结论TAS-102和奥沙利铂协同增强抑制SNU-449细胞的增殖、迁移和侵袭以及促凋亡作用,其机制可能与促进Bax和E-cadherin蛋白以及抑制Bcl-2和Vimentin蛋白表达有关。Objective To investigate the effects of trifluridine-tipiracil hydrochloride tablets(TAS-102)combined with oxaliplatin(L-OHP)on proliferation,migration,invasion and apoptosis of hepatocellular carcinoma SNU-449 cells and its possible mechanism.Methods SNU-449 cells were divided into control group(without drugs),TAS-102 group(2μg·mL^(-1)),oxaliplatin group(1.2μg·mL^(-1))and combination group(2μg·mL^(-1)TAS-102+1.2μg·mL^(-1)L-OHP).Cell counting kit-8 assay was used to detect cell proliferation ability;Transwell assay was used to detect cell migration and invasion;the apoptosis rate was analyzed by flow cytometry;the expressions of B-cell lymphoma-2(Bcl-2),Bcl-2-associated X(Bax),E-cadherin and Vimentin were detected using Western blotting.Results Survival rate of cells in control group,TAS-102 group,oxaliplatin group and combination group were(100.00±2.98)%,(80.26±5.55)%,(78.49±5.76)%and(47.82±4.26)%,respectively;the number of cell migration were 436.83±27.50,228.17±15.87,171.67±19.49 and113.83±11.34,respectively;the number of cell invasion were 332.67±19.95,205.33±13.65,219.67±14.49and 116.83±11.30,respectively;the apoptosis rates were(2.32±0.07)%,(6.74±0.24)%,(6.37±0.18)%and(10.67±0.41)%,respectively;the relative expression levels of Bax protein were 0.28±0.01,0.53±0.03,0.75±0.03 and 1.11±0.03,respectively;the relative expression levels of Bcl-2 protein were 0.65±0.03,0.32±0.02,0.23±0.02 and 0.13±0.01,respectively;the relative expression levels of E-cadherin were0.15±0.01,0.24±0.02,0.35±0.02 and 0.64±0.02,respectively;the relative expression levels of Vimentin were 0.65±0.03,0.27±0.01,0.34±0.02 and 0.18±0.01,respectively.Comparison of each treatment group with the control group and comparison of the combination group with monotherapy group,the above indexes were statistically significant(allP<0.05).Conclusion The synergistic effect of TAS-102 and oxaliplatin enhanced the inhibitionon proliferation,migration,and invasion,and promoted cell apoptosis of SNU-449 cells,and the m

关 键 词：曲氟尿苷替匹嘧啶片 奥沙利铂 肝细胞癌 增殖 迁移 侵袭 凋亡 

分 类 号：R979.1[医药卫生—药品]