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右美托咪定增加分泌型 SERPINE1 表达对甲状腺癌细胞恶性生

          物学行为的影响
                                   Δ


                                           4 #
          童雪燕 ,蒋文锋 ,曾亮平 ,林 燕 (1.上饶市中心医院药剂科,江西 上饶 334000;2.上饶市中心医院手足
                                  3
                          2
                 1*
          显微外科,江西 上饶 334000;3.上饶市中心医院骨科,江西 上饶 334000;4.上饶市人民医院药剂科,江西
          上饶 334000)
          中图分类号  R965;R736.1      文献标志码  A      文章编号  1001-0408(2025)10-1179-07
          DOI  10.6039/j.issn.1001-0408.2025.10.05


          摘  要  目的  探讨右美托咪定(DEX)增加分泌型丝氨酸蛋白酶抑制剂家族E成员1(SERPINE1)蛋白表达对甲状腺癌(THCA)
          细胞恶性生物学行为的影响。方法  使用1、10、100 nmol/L的DEX处理THCA细胞(KTC-1、TPC-1),检测其活力、克隆形成率、迁
          移率和侵袭数。通过全基因组测序和基因本体等富集分析探讨DEX在THCA中的潜在生物学功能;通过蛋白质-蛋白质相互作用
          网络挖掘DEX的核心靶点,并评估DEX核心靶点的表达特征及其与患者预后的关系。检测DEX对2种THCA细胞中核心靶点
          mRNA、蛋白表达及蛋白分泌的影响,通过敲减核心靶点来初步验证该靶点对 DEX 相关作用的影响。结果  与对照(0 nmol/L
          DEX)组比较,1、10、100 nmol/L DEX 组 2 种 THCA 细胞的活力(1 nmol/L DEX 组 KTC-1 细胞 24 h 时除外)均显著升高,克隆形成
          率、迁移率(1 nmol/L DEX 组 2 种 THCA 细胞除外)和侵袭数亦显著升高且呈浓度依赖性(P<0.05)。DEX 处理或不处理的 2 种
          THCA细胞中,共有287个差异表达基因(75个上调、212个下调),富集于磷脂酰肌醇3激酶/蛋白激酶B、Wnt和衰老相关分泌表型
          等信号通路;SERPINE1是DEX促THCA的核心靶点,其mRNA及蛋白在THCA组织/细胞中的表达均显著升高,且与患者的不良
          预后有关(P<0.05);与对照组比较,1、10、100 nmol/L DEX组2种THCA细胞中SERPINE1 mRNA及蛋白的表达均显著上调,且在
          条件培养基中该蛋白的分泌亦显著增多,均呈浓度依赖性(P<0.05)。敲减SERPINE1后,DEX对2种THCA细胞增殖、克隆形成、
          迁移、侵袭能力的促进作用受到了显著抑制(P<0.05)。结论  DEX能够促进THCA细胞的增殖、迁移和侵袭,上述作用可能与增
          加分泌型SERPINE1蛋白的表达有关。
          关键词  右美托咪定;甲状腺癌;SERPINE1;恶性生物学行为

          Effects  of  increased  secretory  SERPINE1  expression  by  dexmedetomidine  on  the  malignant  biological
          behavior of thyroid carcinoma cells
                                                                    4
                       1
          TONG Xueyan ,JIANG Wenfeng ,ZENG Liangping ,LIN Yan (1.  Dept.  of  Pharmacy,  Shangrao  Central
                                                          3
                                        2
          Hospital,  Jiangxi  Shangrao  334000,  China;2.  Dept.  of  Hand  and  Foot  Microsurgery,  Shangrao  Central
          Hospital,  Jiangxi  Shangrao  334000,  China;3.  Dept.  of  Orthopedics,  Shangrao  Central  Hospital,  Jiangxi
          Shangrao 334000, China;4. Dept. of Pharmacy, Shangrao People’s Hospital, Jiangxi Shangrao 334000, China)
          ABSTRACT   OBJECTIVE  To  explore  the  effects  of  dexmedetomidine (DEX)  increasing  serpin  peptidase  inhibitor  clade  E
          member 1 (SERPINE1) protein on the malignant biological behavior of thyroid carcinoma (THCA) cells. METHODS THCA cells
         (KTC-1, TPC-1)  were  treated  with  1,  10  and  100  nmol/L  DEX,  and  their  viabilities,  clone  formation  rates,  migration  rates  and
          invasion  number  were  examined.  Potential  biological  functions  of  DEX  in  THCA  cells  were  analyzed  through  whole  genome
          sequencing  and  gene  ontology  enrichment  analysis.  The  core  targets  of  DEX  were  mined  through  a  protein-protein  interaction
          network. The expression characteristics of DEX core targets and their relationship with patient prognosis were evaluated. The effects
          of  DEX  on  mRNA  and  protein  expressions  of  core  targets  and  protein  secretion  in  2  types  of  THCA  cells  were  detected,  and  the
          effects  of  this  target  on  DEX-related  effects  were  validated  preliminarily  by  knocking  down  the  core  target.  RESULTS  Compared
          with the control group (0 nmol/L DEX), DEX at 1, 10 and 100 nmol/L significantly increased the viabilities of 2 types of THCA
          cells (except  for  the  KTC-1  cells  in  the  1  nmol/L  DEX  group  at  24  h),  concentration-dependently  elevated  the  rates  of  clone
                                                             formation,  migration  rates (except  for  2  types  of  THCA  cells
             Δ 基金项目 江西省卫生健康委科技计划项目(No.202212777,No.
                                                             in  1  nmol/L  DEX  group),  and  the  number  of  invasion (P<
          20197555);上饶市科技计划项目(No.2023CZDX82)                 0.05).  A  total  of  287  differently  expressed  genes (75  up-
             *第一作者 副主任药师。研究方向:药理学、医院药学。E-mail:
          tongxueyan180@163.com                              regulated  and  212  down-regulated)  were  enriched  in  signaling
             # 通信作者 副主任药师。研究方向:药理学、医院药学。E-mail:              pathways  such  as  phosphatidylinositol  3-kinase/protein  kinase
          19581192@qq.com                                    B,  Wnt,  and  senescence-associated  secretory  phenotypes  in


          中国药房  2025年第36卷第10期                                              China Pharmacy  2025 Vol. 36  No. 10    · 1179 ·
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