维生素D3通过Hedgehog信号通路对胰腺癌PANC1细胞增殖与凋亡的影响  

Influence of vitamin D3 on proliferation and apoptosis of PANC1 cells through hedgehog signaling pathway

作　　者：商建[1] 邹金艳[1] 伍威[1] 易三凤[1] 张海平[1] 林军[1] 

机构地区：[1]武汉大学中南医院消化内科武汉大学医学院消化系统疾病研究中心湖北省肠病临床医学研究中心肠病湖北省重点实验室,430071

出　　处：《中华胰腺病杂志》2014年第6期385-388,共4页Chinese Journal of Pancreatology

基　　金：湖北省自然科学基金面上项目（2014CFB747）;武汉市科技计划项目（2014060101010054）

摘　　要：目的 探讨维生素D3抗胰腺癌的作用机制.方法 应用不同浓度的维生素D3（25、50、75、100 μmol/L）干预胰腺癌PANC1细胞,以未干预细胞作为阴性对照组.MTT比色法检测细胞的生长抑制率;流式细胞仪检测细胞的早期凋亡率;RT-PCR法检测细胞PTCH、Gli-1 mRNA的表达.结果 维生素D3呈浓度依赖性抑制PANC1细胞的增殖,以48 h点的抑制作用最强,阴性对照组及25、50、75、100 μmol/L维生素D3组的生长抑制率分别为0、16.1％、18.8％、31.8％、39.4％,组间差异有统计学意义（P值均＜0.05）.阴性对照组及25、50、75、100 μmol/L维生素D3干预24 h时PANC1细胞的早期凋亡率分别为（5.89±0.57）％、（6.06±0.44）％、（16.21± 1.62）％、（16.94±0.91）％、（20.96±0.98）％,早期凋亡率随浓度的增加而增加,差异有统计学意义（P＜0.05）.维生素D3干预PANC1细胞24 h后,阴性对照组及25、50、75、100 μmol/L组细胞的PTCH mRNA表达量分别为0.117±0.009、0.104 ±0.011、0.069±0.011、0.052±0.009、0.056±0.007;Gli-1 mRNA表达量分别为0.323±0.007、0.312±0.015、0.299±0.015、0.233 ±0.007、0.175 ±0.014,均随浓度的增加而下调,差异有统计学意义（P值均＜0.05）.75 μmol/L维生素D3干预0、12、24、36、48 h后,PTCH mRNA表达量分别为0.142±0.008、0.127 ±0.009、0.111±0.010、0.115 ±0.003、0.102±0.007;Gli-1 mRNA分别为0.341±0.011、0.317 ±0.017、0.320±0.018、0.226 ±0.011、0.191±0.010,均随时间的延长而下调,差异有统计学意义（P值均＜0.05）.结论 维生素D3可以有效抑制胰腺癌PANC1细胞的增殖,促进细胞凋亡,其机制可能与阻滞Hedgehog信号通路有关.Objective To investigate the role of vitamin D3 in anti-pancreatic cancer.Methods After treatment of different concentrations of vitamin D3 on PANC1 cells （25,50,75,100μmol/L）,MTT assay was used to detect the growth inhibition rates of PANC1 cells,the early apoptotic rates of the cell were detected by flow cytometry,PTCH and Gli-1 mRNA expression were detected by RT-PCR method,and cells without treatment were used as control.Results The vitamin D3 inhibited the proliferation of PANC1 cells in a dose-dependent manner,the highest inhibition rate was at 48 hours.After 48 hours,the control group,25,50,75,100 μmol/L vitamin D3 groups＆#39; inhibition rates were 0,16.1%,18.8%,31.8% and 39.4%,the differences among these groups were statistically significance （P 〈 0.05）.After 24 hours,the control group,25,50,75,100μmol/L vitamin D3 groups＆#39; early apoptotic rates were （5.89 ±0.57）%,（6.06 ±0.44）%,（16.21 ± 1.62）%,（16.94± 0.91）% and （20.96 ± 0.98）%,early apoptotic rates were inhibited in a dose-dependent manner,and the differences was statistically significance （P 〈 0.05）.After 24 hours,the control group,25,50,75,100μmol/L vitamin D3 groups＆#39; PTCH mRNA expression were 0.117 ± 0.009,0.104 ± 0.011,0.069 ± 0.011,0.052 ± 0.009 and 0.056 ± 0.007,meanwhile the Gli-1 mRNA expressions were 0.323 ± 0.007,0.312 ± 0.015,0.299 ± 0.015,0.233 ± 0.007 and 0.175 ± 0.014,all in a declining trend with the increase of concentration,and the difference was statistically significant （P 〈 0.05）.After 75 μmol/L vitamin D3＆#39;s intervention in 0,12,24,36 and 48 hours,the expression of PTCH mRNA were 0.142±0.008,0.127± 0.009,0.111± 0.010,0.115± 0.003 and 0.102± 0.007,meanwhile the expression of Gli-1 mRNA were 0.341 ± 0.011,0.317 ± 0.017,0.320 ± 0.018,0.226 ± 0.011 and 0.191 ±0.010,all in a declining trend with time,and the difference was statistically significance （p〈0.05）.Conclusions Vitamin D3 can effectively inhibit the proliferation of PANC1 cells and pro

关 键 词：胰腺肿瘤 HEDGEHOG信号通路 细胞增殖 细胞凋亡 

分 类 号：R735.9[医药卫生—肿瘤]