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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
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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 ·