吉西他滨与厄洛替尼联合治疗胰腺癌的试验研究  

Preliminary study of gemcitabine combined with erlotinib in the treatment of pancreatic cancer

作　　者：张强[1] 秦爱玉 秦玉刚[1] ZHANG Qiang;QIN Aiyu;QIN Yugang(Department of Hepatobiliary Surgery,Space Center Hospital,Beijing 100049,China;Department of Emergency,Guangrao Hospital of Traditional Chinese Medicine,Dongying,Shandong 257300,China)

机构地区：[1]航天中心医院肝胆外科,北京100049 [2]广饶县中医院急诊科,山东东营257300

出　　处：《安徽医药》2020年第10期1952-1957,共6页Anhui Medical and Pharmaceutical Journal

摘　　要：目的探究吉西他滨与厄洛替尼联合使用对体外胰腺癌细胞的影响。方法2018年4月至2019年4月,在航天中心医院肝胆外科选用人胰腺癌细胞PANC-1对数生长期细胞。实验分组:厄洛替尼组、吉西他滨组、联合作用组(1∶2、1∶1、2∶1、3∶1),每组设12个培养皿。用八肽胆囊收缩素-8(Cholecystokinin octapeptide-8,CCK-8)法检测吉西他滨及厄洛替尼分别对PANC-1细胞的细胞毒性试验,并计算出两种药物分别对PANC-1细胞的半抑制浓度(50%Inhibiting Concentration,IC50)。根据两种药物对PANC-1的IC50值的影响,按照不同比例重复观察两种药物联合使用对细胞的细胞毒性情况,以中位药效法(Chou-Talalay法)分析两种药物的联合作用效果。用细胞平板克隆形成实验观察吉西他滨,厄洛替尼及两种药物联合作用对胰腺癌细胞PANC-1的细胞克隆形成的影响。结果在给予系列浓度的厄洛替尼和吉西他滨培养液培养胰腺癌PANC-1细胞后,在一定时间内,不同浓度的吉西他滨和厄洛替尼均能抑制PANC-1细胞增殖,并且抑制作用随浓度增加而增强,且一定浓度下,药物处理时间越长,抑制作用越强(128 n M厄洛替尼浓度72 h细胞抑制率为(76.72±5.51)%;320 nM吉西他滨浓度72 h细胞抑制率为(75.43±0.97)%。吉西他滨和厄洛替尼对胰腺癌PANC-1细胞生长的影响具有时间-浓度依赖性。通过IC50计算软件计算药物处理48 h时的IC50值,结果显示厄洛替尼对PANC-1的IC50值为12 nM,吉西他滨对PANC-1的IC50值为80 nM。厄洛替尼和吉西他滨联合使用可以增大细胞抑制率,减少单独使用吉西他滨的起效时间[厄洛替尼∶吉西他滨为3∶1时,72h细胞抑制率为(89.89±1.56)%,IC50值为(3.89±1.65)nmol/L]。随着细胞生长抑制率的增加,CI值逐渐下降。当细胞生长抑制率达到35%时,联合效应开始出现协同作用(小于0.9)。当细胞生长抑制率为40%时,CI下降(均小于0.5),具有的协同作用。同时,Objective To explore the effect of gemcitabine and erlotinib on pancreatic cancer.MethodsHuman pancreatic cancer cells PANC-1 in the logarithmic phase in the Department of Hepatobiliary Surgery,Space Center Hospital from April 2018 to April2019 were selected.Experimental groups:erlotinib group,gemcitabine group,combined group(1∶2,1∶1,2∶1,3∶1),each group with12 culture dishes.The cytotoxicity of gemcitabine and erlotinib on PANC-1 cells was detected by Cholecystokinin octapeptide-8(CCK-8)assay.The half inhibition concentration(IC50)values of gemcitabine and erlotinib on PANC-1 cells were calculated.According to the influence of the two drugs on the IC50 value of PANC-1,the cytotoxicity of the two drugs on the cells was observed repeatedly according to different proportions,and the combined effect of the two drugs was analyzed by the median pharmacodynamic(Chou Talalay)method.The effect of gemcitabine,erlotinib and combination of gemcitabine and erlotinib on the colony formation of PANC-1 cells was observed by cell plate clone formation assay.ResultsAfter a series of concentrations of erlotinib and gemcitabine were given to culture pancreatic cancer PANC-1 cells,the different concentrations of gemcitabine and erlotinib could inhibit the proliferation of PANC-1 cells within a certain period of time,and the inhibitory effect increased with the increase of concentration.At a certain concentration,the longer the drug treatment time was,the stronger the inhibitory effect[72 h cell inhibition rate of 128 nM erlotinib and 320 nM gemcitabine concentration is(76.72±5.51)%and(75.43±0.97)%,respectively].The effects of gemcitabine and erlotinib on the growth of pancreatic cancer PANC-1 cells were time and concentration dependent.The IC50 values of erlotinib and gemcitabine were 12 nM and 80 nM,respectively.The combination of erlotinib and gemcitabine can increase the cell inhibition rate and reduce the onset time of gemcitabine alone[erlotinib:gemcitabine=3∶1,72 h cell inhibition rate was(89.89±1.56)%,and IC50 val

关 键 词：胰腺肿瘤 吉西他滨 厄洛替尼 细胞增殖 半数抑制浓度 克隆细胞 

分 类 号：R735.9[医药卫生—肿瘤]