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异鼠李素通过上调SLC25A25-AS1对胃癌发展的影响                                                       Δ



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          张 洋 ,王 静 ,那丽莎 ,曾傲然 ,庞博文 ,刘禹麟(1. 牡丹江医科大学附属红旗医院检验科,黑龙江
                 1*
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          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)
          中图分类号  R965;R735.2      文献标志码  A      文章编号  1001-0408(2025)08-0932-07
          DOI  10.6039/j.issn.1001-0408.2025.08.07

          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(70 μmol/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、
          PTEN mRNA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、48 h)、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 表达、下调 miR-
          212-3p并上调miR-212-3p下游靶点PTEN的表达,从而抑制胃癌的发展。
          关键词  异鼠李素;胃癌;SLC25A25-AS1;miR-212-3p;PTEN

          Effects of isorhamnetin on the development of gastric cancer by up-regulating SLC25A25-AS1
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          ZHANG Yang ,WANG Jing ,NA Lisha ,ZENG Aoran ,PANG Bowen ,LIU Yulin (1.  Dept.  of  Clinical
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          Laboratory,  Hongqi  Hospital  Affiliated  to  Mudanjiang  Medical  University,  Heilongjiang  Mudanjiang  157011,
          China;2.  Biology  Teaching  and  Research  Office,  School  of  Basic  Medicine,  Mudanjiang  Medical  University,
          Heilongjiang  Mudanjiang  157011,  China;3.  Dept.  of  Pharmacy,  Hongqi  Hospital  Affiliated  to  Mudanjiang
          Medical University, Heilongjiang Mudanjiang 157011, China)
          ABSTRACT    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 (70  μmol/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
              Δ 基金项目 黑龙江省自然科学基金项目(No.LH2021C097)              in  isorhamnetin-treated  cells  were  investigated.  RESULTS
             *第一作者 中级检验技师。研究方向:血液肿瘤细胞学检测技
                                                              Compared  with  the  model  control  group,  tumor  volume  and
          术。E-mail:18704532743@163.com
              # 通信作者 讲师,博士研究生。研究方向:恶性肿瘤发生与防治                  mass of nude mice in the isorhamnetin low-dose and high-dose
          的分子机制。E-mail:wangjing181719@163.com                 groups  were  reduced  significantly,  and  the  isorhamnetin  high-


          · 932 ·    China Pharmacy  2025 Vol. 36  No. 8                               中国药房  2025年第36卷第8期
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