奥曲肽联合黄芩素抑制胰腺神经内分泌肿瘤细胞增殖和迁移  

Octreotide Combined with Baicalein Inhibits the Proliferation and Migration of Pancreatic Neuroendocrine Neoplasms

作　　者：陈挑调 柏建安 叶木杰 严丽军[1,2] 潘佳玲 汤琪云 CHEN Tiao-tiao;BAI Jian-an;YE Mu-jie;YAN Li-jun;PAN Jia-ling;TANG Qi-yun(Department of Geriatric Gastroenterology,the First Affiliated Hospital of Nanjing Medical University,Nanjing,Jiangsu,210029 China;Institute of Neuroendocrine Tumor,Nanjing Medical University,Nanjing,Jiangsu,210029,China)

机构地区：[1]南京医科大学第一附属医院老年消化科,江苏南京210029 [2]南京医科大学神经内分泌肿瘤研究所,江苏南京210029

出　　处：《现代生物医学进展》2022年第12期2201-2207,共7页Progress in Modern Biomedicine

基　　金：国家自然科学基金青年基金项目(82003256);江苏省第五期"333"工程项目(BRA2017535)。

摘　　要：目的:探讨奥曲肽(Octreotide,Oct)联合黄芩素(Baicalein,BE)对胰腺神经内分泌肿瘤(Pancreatic neuroendocrine neoplasms,p NENs)的影响。方法:用不同浓度的奥曲肽和黄芩素处理pNENs来源的QGP-1细胞,CCK8法检测细胞的存活率,以其半抑制浓度(IC_(50))的比值作为浓度梯度进行联合用药,并用Compusyn软件进行联合指数(CI)分析,取细胞毒性效应适中且CI值较低的浓度(奥曲肽150μmol/L,黄芩素20μmol/L)进行表型实验。将QGP-1细胞分为四组:对照组、奥曲肽组、黄芩素组、奥曲肽和黄芩素联用组。通过克隆形成实验、EdU增殖检测、划痕实验、细胞凋亡和周期检测评价四组细胞的增殖、迁移能力以及凋亡和细胞周期的情况。结果:药物处理24 h后,奥曲肽和黄芩素均能够呈浓度依赖性抑制QGP-1细胞增殖(P<0.05),奥曲肽的IC_(50)为329.90μmol/L,黄芩素的IC_(50)为42.86μmol/L,两者IC_(50)的比值约为7.5:1,联用组细胞活性明显低于单药组(P<0.05),且CI值随着药物浓度的增加而降低。克隆形成实验和EdU增殖检测结果表明,奥曲肽和黄芩素均可抑制QGP-1细胞增殖(P<0.05),且联用组的克隆形成率和EdU阳性细胞百分比均低于单药组(P<0.05)。划痕实验结果表明,奥曲肽和黄芩素均可降低QGP-1细胞的迁移率(P<0.05),且联用组的迁移率低于单药组(P<0.05)。细胞凋亡和周期检测结果表明,黄芩素可促进QGP-1细胞的凋亡(P<0.05),并使QGP-1细胞阻滞于G0/G1期(P<0.05),而奥曲肽对QGP-1细胞的凋亡和细胞周期无明显影响(P>0.05),两药联用对其凋亡和周期无协同作用。结论:奥曲肽和黄芩素联合用药可协同抑制QGP-1细胞增殖和迁移,对细胞凋亡和周期无明显协同作用。Objective:To investigate the effect of octreotide combined with baicalein inhibits the proliferation and migration of pancreatic neuroendocrine neoplasms(pNENs).Methods:QGP-1 cells derived from pNENs were treated with different concentrations of octreotide and baicalein,and cell viability was detected by CCK8.The ratio of semi-inhibitory concentration(IC_(50))was used as the concentration gradient for combination drugs.The combination index(CI)analysis was analyzed by Compusyn software,and the concentrations with moderate cytotoxicity and low CI value(octreotide 150μmol/L,baicalein 20μmol/L)were selected for phenotypic experiments.QGP-1 cells were divided into four groups:control group,octreotide group,baicalein group and combined group.The proliferation,migration,apoptosis and cell cycle of the four groups were evaluated by colony formation assay,EdU proliferation assay,wound healing assay,apoptosis and cell cycle assay.Results:After 24 hours of treatment,octreotide and baicalein could inhibit the proliferation of QGP-1 cells in a concentration-dependent manner(P<0.05).The IC_(50)of octreotide was 329.90μmol/L,the IC_(50)of baicalein was 42.86μmol/L,and the ratio of IC_(50)was 7.5:1.The cell viability in the combined group was significantly lower than that in the single drug group(P<0.05),and the CI value decreased with the increase of drug concentration.The results of colony formation assay and Ed U proliferation assay showed that both octreotide and baicalein could inhibit the proliferation of QGP-1 cells(P<0.05),and the colony formation rate and the percentage of EdU positive cells in the combination group were lower than those in the single drug group(P<0.05).The results of wound healing assay showed that both octreotide and baicalein could reduce the migration rate of QGP-1 cells(P<0.05),and the migration rate in the combination group was lower than that in the single drug group(P<0.05).The results of apoptosis and cell cycle assay showed that baicalein could promote the apoptosis of QGP-1 cells(P<0.05)

关 键 词：胰腺神经内分泌肿瘤 奥曲肽 黄芩素 增殖 迁移 

分 类 号：R-33[医药卫生] R735.9R979.1