| 张强,秦爱玉,秦玉刚.吉西他滨与厄洛替尼联合治疗胰腺癌的试验研究[J].安徽医药,2020,24(10):1952-1957. |
| 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 |
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| DOI：10.3969/j.issn.1009?6469.2020.10.009 |
| 中文关键词: 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 |
| 英文关键词: Pancreatic neoplasms Gemcitabine Erlotinib Cell proliferation 50% Inhibitory concentration Clone cells |
| 基金项目: |
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| 中文摘要: |
| 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 nM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， 2∶1组曲 |
| 英文摘要: |
| Objective To explore the effect of gemcitabine and erlotinib on pancreatic cancer.Methods Human pancreatic cancer cells PANC?1 in the logarithmic phase in the Department of Hepatobiliary Surgery，Space Center Hospital from April 2018 to April 2019 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.Ac?cording 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 pharmacodynam? ic(Chou Talalay)method.The effect of gemcitabine，erlotinib and combination of gemcitabine and erlotinib on the colony formationof PANC?1 cells was observed by cell plate clone formation assay.Results After a series of concentrations of erlotinib and gem? citabine were given to culture pancreatic cancer PANC?1 cells，the different concentrations of gemcitabine and erlotinib could inhib?it the proliferation of PANC?1 cells within a certain period of time，and the inhibitory effect increased with the increase of concen? tration.At a certain concentration，the longer the drug treatment time was，the stronger the inhibitory effect［72h cell inhibition rate of 128nM erlotinib and 320nM 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 valuesof erlotinib and gemcitabine were 12nM and 80nM，respectively.The combination of erlotinib and gemcitabine can increase the cellinhibition 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 value was(3.89 ± 1.65)nmol/L］.With the increase of cell growth inhibition rate，CI value decreased gradually. When the cell growth inhibition rate reached 35%，the synergistic effect began to appear(less than 0.9).When the cell growth inhi? bition rate was 40%，CI decreased(all less than 0.5)，which had a synergistic effect.At the same time，the 2:1 group curve was low? er than the 3∶1 group curve，indicating that the synergistic effect of erlotinib and gemcitabine concentration ratio of 2∶1 was better than the concentration ratio of 3:1.The number of cells in control group was 361，the number of cells in erlotinib alone group was 128；the number of cells in gemcitabine group was 114，and the number of cells in combined treatment group(1∶2，1∶1，2∶1，3∶1) was 118，98，76 and 80.Conclusions Gemcitabine and erlotinib alone can inhibit the growth of human pancreatic cancer cells invitro and play a role in inhibiting pancreatic cancer.The combined use of the two drugs can reduce the dosage of the two drugs andplay a synergistic role to achieve and improve the effect of suppressing pancreatic cancer tumor cells proliferation. |
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