程序性死亡受体-配体1抑制药联合洛铂对卵巢癌细胞上皮间质转化的作用  

Effect of programmed death receptor-ligand 1 inhibitor combined with lobaplatin on epithelial-mesenchymal transition of ovarian cancer cells

作　　者：苏伟平 吕玉琼[1] 李鲁宏[1] SU Wei-ping;LÜYu-qiong;LI Lu-hong(Department of Obstetrics and Gynecology,The Second Affiliated Hospital of Fujian Medical University,Quanzhou 362000,Fujian Province,China)

机构地区：[1]福建医科大学附属第二医院妇产科,福建泉州362000

出　　处：《中国临床药理学杂志》2023年第16期2353-2357,共5页The Chinese Journal of Clinical Pharmacology

摘　　要：目的探究抑制程序性死亡受体-配体1(PD-L1)表达联合洛铂对卵巢癌细胞上皮间质转化(EMT)的影响及其可能的作用机制。方法体外培养人卵巢癌SKOV3细胞,并将细胞分为对照组(不做处理)、洛铂组(0.5μg·mL^(-1)洛铂处理24 h)、洛铂+NC组(转染NC inhibitor慢病毒质粒后使用0.5μg·mL^(-1)的洛铂处理细胞24 h)和洛铂+inhibitor组(转染PD-L1 inhibitor慢病毒质粒后使用0.5μg·mL^(-1)的洛铂处理细胞24 h)。用细胞计数试剂盒8(CCK-8)检测细胞存活率;用平板克隆形成实验检测细胞增殖;用蛋白质印迹(Western blot)法检测细胞相关蛋白表达情况;用TUNEL法检测细胞凋亡率。结果对照组、铂组、洛铂+NC组、洛铂+inhibitor组细胞克隆形成数分别为(443.45±24.37)、(271.46±20.44)、(268.38±19.98)和(126.35±14.26)个,增殖细胞核抗原(PCNA)蛋白表达水平分别为0.95±0.07、0.70±0.08、0.71±0.06和0.38±0.04,TUNEL阳性细胞率分别为(4.06±0.31)%、(9.39±0.52)%、(9.68±0.49)%、(20.37±1.67)%,上皮细胞钙粘蛋白(E-cadherin)蛋白水平分别为0.31±0.05、0.52±0.05、0.53±0.04和0.91±0.07,N-钙黏着蛋白(N-cadherin)蛋白表达水平分别为0.98±0.10、0.70±0.07、0.68±0.08和0.29±0.04,磷酸化Janus激酶2(p-JAK2)蛋白水平分别为0.88±0.07、0.65±0.04、0.63±0.05和0.31±0.04,洛铂组、洛铂+NC组、洛铂+inhibitor组上述指标与对照组比较,差异均有统计学意义(均P<0.05),洛铂+inhibitor组上述指标与洛铂组、洛铂+NC组比较,差异均有统计学意义(均P<0.05)。结论PD-L1抑制药联合洛铂可显著抑制细胞增殖、EMT并诱导凋亡,这可能与抑制JAK2/信号转导与转录激活因子3(STAT3)通路有关。Objective To investigate the effect of inhibiting programmed death receptor-ligand 1(PD-L1)expression combined with lobaplatin on epithelial-mesenchymal transition(EMT)of ovarian cancer cells and its possible mechanism.Methods Human ovarian cancer SKOV3 cells were cultured in vitro and divided into control group(no treatment),LOB group(0.5μg·mL^(-1) lobaplatin treatment for 24 h),LOB+NC group(0.5μg·mL^(-1) lobaplatin treatment for 24 h after transfection of NC inhibitor lentiviral plasmid)and LOB+inhibitor group(0.5μg·mL^(-1) lobaplatin treatment for 24 h after transfection of PD-L1 inhibitor lentiviral plasmid).Cell viability was detected by cell counting kit 8(CCK-8).Cell proliferation was detected by plate clone formation assay.The expression of cell-related proteins in each group was detected by Western blot.The apoptosis rate of each group was detected by TUNEL method.Results The number of cell clonal formation number in control group,LOB group,LOB+NC group and LOB+inhibitor group were 443.45±24.37,271.46±20.44,268.38±19.98 and 126.35±14.26,respectively;the expression levels of PCNA protein were 0.95±0.07,0.70±0.08,0.71±0.06 and 0.38±0.04,respectively;TUNEL positive cell rates were(4.06±0.31)%,(9.39±0.52)%,(9.68±0.49)%and(20.37±1.67)%,respectively;E-cadherin protein levels were 0.31±0.05,0.52±0.05,0.53±0.04 and 0.91±0.07,respectively;the expression levels of N-cadherin protein were 0.98±0.10,0.70±0.07,0.68±0.08 and 0.29±0.04,respectively;the protein levels of p-JAK2 were 0.88±0.07,0.65±0.04,0.63±0.05 and 0.31±0.04,respectively.Compared with the control group,the above indexes in LOB group,LOB+NC group and LOB+inhibitor group were significantly different(all P<0.05),compared with LOB group and LOB+NC group,there were statistically significant differences in the above indexes in LOB+inhibitor group(all P<0.05).Conclusion PD-L1 inhibitor combined with lobaplatin can significantly inhibit cell proliferation,EMT and induce apoptosis,which may be related to the inhibition of JAK2/sign

关 键 词：洛铂 程序性死亡受体-配体1抑制药 卵巢癌 上皮间质转化 Janus激酶2/信号转导与转录激活因子3通路 

分 类 号：R979.1[医药卫生—药品]