吉西他滨联合热疗对胰腺癌PANC-1细胞凋亡的影响及机制研究  

Effect and mechanism of gemcitabine combined with hyperthermia on apoptosis of pancreatic cancer PANC-1 cells

作　　者：习攀 王蒨 郭俊俊 李量 张璞 XI Pan;WANG Qian;GUO Junjun;LI Liang;ZHANG Pu(Department of Radiotherapy,Shaanxi Provincial Cancer Hospital,Xi’an 710061,China)

机构地区：[1]陕西省肿瘤医院放疗科,陕西西安710061 [2]陕西省核工业二一五医院胸外科,陕西咸阳712000

出　　处：《陕西医学杂志》2023年第9期1130-1134,共5页Shaanxi Medical Journal

基　　金：陕西省卫生健康委员会科研基金资助项目(2022D046)。

摘　　要：目的:探索吉西他滨(GEM)联合热疗对胰腺癌PANC-1细胞凋亡的影响及机制。方法:将人胰腺癌PANC-1细胞随机分为对照组(无任何处理)、GEM组(给予GEM)和热化疗组(给予热疗联合GEM)。比较各组细胞增殖、凋亡、活性氧(ROS)、特异性蛋白1(Sp1)及其下游蛋白表达情况。评估ROS抑制剂N-乙酰半胱氨酸(NAC)对各组细胞增殖及相关蛋白表达的影响。结果:GEM对PANC-1细胞增殖的抑制作用呈剂量和时间依赖性。30μmol/L GEM对PANC-1细胞增殖的抑制作用高于其他剂量(均P<0.05)。在GEM治疗前热疗1 h细胞存活率显著低于GEM与热疗同时1 h和GEM治疗后热疗1 h(均P<0.05)。与对照组比较,GEM组和热化疗组细胞凋亡率增加,且热化疗组高于GEM组(均P<0.05)。与对照组比较,GEM组和热化疗组ROS升高,且热化疗组高于GEM组(均P<0.05)。与对照组比较,GEM组和热化疗组Sp1、B细胞淋巴瘤-2(Bcl-2)蛋白表达水平降低,且热化疗组低于GEM组(均P<0.05)。与GEM组比较,热化疗组环氧合酶-2(Cox-2)蛋白表达水平降低(P<0.05)。加入NAC后热化疗组细胞存活率较加入前升高,30μmol/L NAC对PANC-1细胞增殖的影响更显著(均P<0.05)。30μmol/L NAC显著恢复了Sp1及其下游Cox-2和Bcl-2蛋白的表达(均P<0.05)。结论:GEM联合热疗通过诱导ROS的产生抑制胰腺癌PANC-1细胞增殖,促进细胞凋亡,进而抑制Sp1及其下游相关蛋白的表达。Objective:To explore the effect and mechanism of gemcitabine(GEM)combined with hyperthermia on apoptosis of pancreatic cancer PANC-1 cells.Methods:Human pancreatic cancer PANC-1 cells were randomly divided into control group(without any treatment),GEM group(treated with GEM)and thermochemotherapy group(treated with hyperthermia combined with GEM).Cell proliferation,apoptosis,reactive oxygen species(ROS),specific protein 1(Sp1)and its downstream protein expression were compared among the groups.The effects of ROS inhibitor N-acetylcysteine(NAC)on cell proliferation and related protein expression were evaluated.Results:GEM inhibited the proliferation of PANC-1 cells in a dose-and time-dependent manner.The inhibitory effect of 30μmol/L GEM on the proliferation of PANC-1 cells was higher than that of other doses(all P<0.05).The cell survival rate of hyperthermia for 1 hour before GEM treatment was significantly lower than that of both GEM and hyperthermia for 1 hour and that of hyperthermia for 1 hour after GEM treatment(all P<0.05).Compared with the control group,the apoptosis rate of GEM group and thermochemotherapy group was increased,and the thermochemotherapy group was higher than GEM group(all P<0.05).Compared with the control group,ROS level was increased in the GEM group and the thermochemotherapy group,and the thermochemotherapy group was higher than GEM group(all P<0.05).Compared with the control group,the protein expression levels of Sp1 and Bcl-2 in the GEM group and the thermochemotherapy group were decreased,and the thermochemotherapy group was lower than GEM group(all P<0.05).Compared with the GEM group,the expression of cyclooxygenase-2(Cox-2)protein was decreased in the thermochemotherapy group(P<0.05).After the addition of NAC,the survival rate of PANC-1 cells in the thermochemotherapy group was higher than that before the addition of NAC,and the effect of 30μmol/L NAC on the proliferation of PANC-1 cells was more significant(all P<0.05).30μmol/L NAC significantly restored the protein expressions

关 键 词：胰腺癌 热疗 吉西他滨 细胞凋亡 活性氧 特异性蛋白1 

分 类 号：R735.9[医药卫生—肿瘤]