摘要
目的观察^(125)I粒子对人肝外胆管癌QBC939细胞增殖、凋亡以及PI3K/AKT信号通路的影响。方法体外培养人胆管癌QBC939细胞,对其分组:0个粒子组(control组)、1个失效粒子组(SX组)、1个有效粒子组(LZ1组)、2个有效粒子组(LZ2组)和3个有效粒子组(LZ3组),各组使用对应数目的^(125)I粒子进行处理。采用集落形成实验、CCK-8实验检测细胞增殖情况;用AnnexinⅤ-FITC/PI双染法来检测各组细胞的凋亡情况;采用Western blot检测各组细胞PI3K/AKT信号通路中关键蛋白AKT、p-AKT、PI3K、p-PI3K、MDM2的表达情况。接种各组细胞制备裸鼠皮下移植瘤模型,观察^(125)I粒子对细胞移植瘤生长的影响。结果与control组相比,LZ1组、LZ2组和LZ3组细胞增殖能力明显下降,且抑制效果随粒子数目增加而不断增强(P<0.05),集落克隆显著减少(P<0.05),细胞凋亡率明显升高(P<0.05);蛋白印迹实验表明相较于control组,LZ1组、LZ2组和LZ3组细胞中AKT、p-AKT、PI3K、p-PI3K、MDM2蛋白的表达水平显著降低(P<0.05)。裸鼠皮下成瘤模型的体内实验结果表明,^(125)I粒子显著抑制了瘤体的生长(P<0.05)。结论^(125)I粒子照射抑制肝外胆管癌QBC939细胞增殖并诱导其凋亡,上述作用可能与PI3K/AKT信号通路受抑相关。
Objective To observe the effects of ^(125)I seeds on the proliferation,the apoptosis and PI3K/AKT signaling pathway of human bile duct carcinoma QBC939 cells.Methods Human cholangiocarcinoma QBC939 cells were cultured in vitro and divided into zero particle group(control group),one invalid particle group(SX group),one valid particle group(LZ1 group),two valid particle group(LZ2 group)and three valid particle group(LZ3 group),and the corresponding number of ^(125)I particles were used to treat the cells in each group.The proliferation of QBC939 cells was detected by colony formation assay and CCK-8 assay.The apoptosis of bile duct cancer cells was detected by AnnexinⅤ-FITC/PI double staining method.Western blot was used to detect the effects of ^(125)I seeds with different gradients on the protein expression of key proteins AKT,P-Akt,PI3K,P-PI3K and MDM2 in PI3K/AKT signaling pathway in QBC939 cells.Cells in each group were inoculated to prepare subcutaneous xenograft tumor models of nude mice,and the effects of ^(125)I seeds on the growth of cell xenograft tumor were observed.Results Compared with control group,the proliferation ability of cells was significantly decreased in LZ1 group,LZ2 group and LZ3 group(P<0.05),and the inhibitory effect was increased with the increase of particle number(P<0.05),the colony cloning was significantly decreased(P<0.05),and the apoptosis rate was significantly increased(P<0.05).Western blot results showed that compared with control group,the protein expression levels of AKT,P-Akt,PI3K,P-PI3K and MDM2 in LZ1 group,LZ2 group and LZ3 group were significantly decreased(P<0.05).In vivo experiment results showed that ^(125)I seeds significantly inhibited the tumor growth in nude mice(P<0.05).Conclusion ^(125)I seed irradiation can inhibit the proliferation and induce the apoptosis of extrahepatic cholangiocarcinoma QBC939 cells,which may be related to the inhibition of PI3K/AKT signaling pathway.
作者
瞿康林
周帅
庞青
李进昂
陈石磊
胡小四
张懿刚
金浩
朱超
王勇
刘会春
QU Kanglin;ZHOU Shuai;PANG Qing;LI Jin’ang;CHEN Shilei;HU Xiaosi;ZHANG Yigang;JIN Hao;ZHU Chao;WANG Yong;LIU Huichun(Department of Hepatobiliary Surgery,First Affiliated Hospital of Bengbu Medical College,Bengbu 233000,China;Fourth Department of General Surgery,Second People’s Hospital of Anhui Province)
出处
《山西医科大学学报》
CAS
2022年第1期19-25,共7页
Journal of Shanxi Medical University
基金
安徽省学术和技术带头人及后备人选科研活动经费资助项目(20180194)
安徽省自然科学基金杰出青年项目(2008085J37)
安徽医科大学临床科学基金项目(2021xkj239)
蚌埠医学院研究生科研创新计划项目(Byycxz21078)。
