异鼠李素通过上调SLC25A25-AS1对胃癌发展的影响  

Effects of isorhamnetin on the development of gastric cancer by up-regulating SLC25A25-AS1

作　　者：张洋 王静 那丽莎 曾傲然 庞博文 刘禹麟 ZHANG Yang;WANG Jing;NA Lisha;ZENG Aoran;PANG Bowen;LIU Yulin(Dept.of Clinical Laboratory,Hongqi Hospital Affiliated to Mudanjiang Medical University,Heilongjiang Mudanjiang 157011,China;Biology Teaching and Research Office,School of Basic Medicine,Mudanjiang Medical University,Heilongjiang Mudanjiang 157011,China;Dept.of Pharmacy,Hongqi Hospital Affiliated to Mudanjiang Medical University,Heilongjiang Mudanjiang 157011,China)

机构地区：[1]牡丹江医科大学附属红旗医院检验科,黑龙江牡丹江157011 [2]牡丹江医科大学基础医学院生物学教研室,黑龙江牡丹江157011 [3]牡丹江医科大学附属红旗医院药学部,黑龙江牡丹江157011

出　　处：《中国药房》2025年第8期932-938,共7页China Pharmacy

基　　金：黑龙江省自然科学基金项目(No.LH2021C097)。

摘　　要：目的探究异鼠李素通过上调溶质载体家族25成员25反义RNA1(SLC25A25-AS1)对胃癌发展的影响。方法以BALB/c裸鼠为对象,通过腋下接种人胃癌细胞MKN28细胞构建移植瘤模型,考察低、高剂量异鼠李素(20、40 mg/kg)对裸鼠瘤体体积及质量的影响。以MKN28细胞为对象,将其分为对照组、异鼠李素(70μmol/L,下同)组、异鼠李素+敲减阴性对照组、异鼠李素+敲减SLC25A25-AS1组、异鼠李素+过表达阴性对照组、异鼠李素+过表达SLC25A25-AS1组,考察敲减/过表达SLC25A25-AS1对异鼠李素处理细胞活力、凋亡、迁移和侵袭能力的影响;验证微RNA-212-3p(miR-212-3p)与SLC25A25-AS1、第10号染色体缺失的磷酸酶及张力蛋白同源物(PTEN)的靶向关系,进一步考察敲减/过表达SLC25A25-AS1对异鼠李素处理细胞中miR-212-3p、PTENmRNA及蛋白表达的影响。结果与模型对照组比较,异鼠李素低、高剂量组裸鼠的瘤体体积及质量均显著降低,且异鼠李素高剂量组显著低于异鼠李素低剂量组(P<0.05)。miR-212-3p与SLC25A25-AS1、PTEN存在靶向关系。与对照组比较,异鼠李素组、异鼠李素+敲减阴性对照组和异鼠李素+过表达阴性对照组的细胞活力(干预24、48h)、迁移细胞数、侵袭细胞数、miR-212-3p的表达均显著降低或减少或下调,凋亡率、PTEN mRNA及蛋白的表达均显著升高或上调(P<0.05);与异鼠李素组和异鼠李素+敲减阴性对照组比较,异鼠李素+敲减SLC25A25-AS1组的细胞活力、迁移细胞数、侵袭细胞数、miR-212-3p的表达均显著升高或增多或上调,凋亡率、PTEN mRNA及蛋白的表达均显著降低或下调(P<0.05);与异鼠李素组和异鼠李素+过表达阴性对照组比较,异鼠李素+过表达SLC25A25-AS1组的细胞活力、迁移细胞数、侵袭细胞数、miR-212-3p的表达均显著降低或减少或下调,凋亡率、PTEN mRNA及蛋白的表达均显著升高或上调(P<0.05)。结论异鼠李素可能通过上调SLC25A25-AS1表OBJECTIVE To explore the effects of isorhamnetin on the development of gastric cancer through up-regulation of solute carrier family 25 member 25 antisense RNA 1(SLC25A25-AS1).METHODS Using BALB/c nude mice as the subjects,the xenograft tumor model was established by subcutaneously inoculating human gastric cancer MKN28 cells into the axillary region.The effects of low and high doses of isorhamnetin(20 and 40 mg/kg)on the tumor volume and mass in nude mice were investigated.MKN28 cells were selected and divided into control group,isorhamnetin group(70μmol/L,similarly hereinafter),isorhamnetin+knocking down negative control group,isorhamnetin+knocking down SLC25A25-AS1 group,isorhamnetin+overexpression negative control group and isorhamnetin+overexpressing SLC25A25-AS1 group.Effects of knocking down/overexpressing SLC25A25-AS1 on viability,apoptosis,migration and invasion ability of isorhamnetin-treated cells were detected.After verifying the targeting relationships between microRNA-212-3p(miR-212-3p)and SLC25A25-AS1,as well as phosphatase and tensin homologue deleted on chromosome 10(PTEN),the effects of knocking down/overexpressing SLC25A25-AS1 on the expression of miR-212-3p,PTEN mRNA,and PTEN protein in isorhamnetin-treated cells were investigated.RESULTS Compared with the model control group,tumor volume and mass of nude mice in the isorhamnetin low-dose and high-dose groups were reduced significantly,and the isorhamnetin high-dose group was significantly lower than the isorhamnetin low-dose group(P<0.05).miR-212-3p had targeting relationships with SLC25A25-AS1 and PTEN.Compared with the control group,the cell viability(intervened for 24,48 h),migration number,invasion number and miR-212-3p expression of cells in the isorhamnetin group,isorhamnetin+knocking down negative control group and isorhamnetin+overexpressing negative control group were significantly reduced or decreased or down-regulated,while the apoptosis rate,mRNA and protein expressions of PTEN were significantly increased or up-regulated(P<0.05)

关 键 词：异鼠李素 胃癌 SLC25A25-AS1 miR-212-3p PTEN 

分 类 号：R965[医药卫生—药理学] R735.2[医药卫生—药学]