扁蒴藤素提高人食管鳞状细胞癌耐药细胞株ECA109/DDP的顺铂敏感性

doi:10.16352/j.issn.1001-6325.2026.09.1200

基础医学与临床 ›› 2026, Vol. 46 ›› Issue (9): 1200-1206.doi: 10.16352/j.issn.1001-6325.2026.09.1200

扁蒴藤素提高人食管鳞状细胞癌耐药细胞株ECA109/DDP的顺铂敏感性

刘桂举, 袁威, 吕鼎霖, 韩倩倩, 梅家转^*, 张浩哲

郑州人民医院肿瘤内科,河南郑州 450000

收稿日期:2025-07-20 修回日期:2025-11-26 出版日期:2026-09-05 发布日期:2026-08-18
通讯作者: ^*mjzhuan@163.com
基金资助:
河南省医学科技攻关计划联合共建项目(LHGJ20230723)

Pristimerin sensitizes human esophageal squamous cell carcinoma cell strain ECA109/DDP to cisplatin

LIU Guiju, YUAN Wei, LYU Dinglin, HAN Qianqian, MEI Jiazhuan^*, ZHANG Haozhe

Department of Medical Oncology, People′s Hospital of Zhengzhou, Zhengzhou 450000, China

Received:2025-07-20 Revised:2025-11-26 Online:2026-09-05 Published:2026-08-18
Contact: ^*mjzhuan@163.com

摘要/Abstract

摘要： 目的探讨扁蒴藤素对食管鳞状细胞癌细胞系ECA109顺铂(DDP)敏感性的作用机制。方法 20 μg/mL DDP处理ECA109细胞,每2~3代递增药物浓度(40、80、100 μg/mL),持续3~6个月直至细胞在高浓度DDP(80 μg/mL)下稳定增殖,即获得DDP稳定耐药株ECA109/DDP。将ECA109/DDP细胞分为对照组(溶剂对照)、DDP(80 μg/mL)组、扁蒴藤素(1 μmol/L)组、扁蒴藤素(1 μmol/L)+DDP(80 μg/mL)组、扁蒴藤素(1 μmol/L)+DDP(80 μg/mL)+TGF-β激活剂(SRI-011381)(10 μmol/L)组。CCK-8法和集落形成实验检测细胞增殖;流式细胞测量术检测细胞凋亡;划痕实验、Transwell小室法分别检测细胞迁移、侵袭;Western blot检测细胞多药耐药相关蛋白1(MRP1)、P-糖蛋白(P-gp)、转化生长因子-β1(TGF-β1)、Smad4、CD44蛋白表达。结果与对照组相比,DDP组各指标差异无统计学意义,扁蒴藤素组A₄₅₀值、集落形成率、划痕愈合率、细胞侵袭数减少(P＜0.05);MRP1、P-gp、TGF-β1、Smad4、CD44蛋白表达降低,细胞凋亡率增加(P＜0.05);与DDP组、扁蒴藤素组相比,扁蒴藤素+DDP组A₄₅₀值、集落形成率、划痕愈合率、细胞侵袭数减少,MRP1、P-gp、TGF-β1、Smad4、CD44蛋白表达降低,细胞凋亡率增加(P＜0.05);与扁蒴藤素+DDP组相比,扁蒴藤素+DDP+SRI-011381组上述指标变化趋势相反(P＜0.05)。结论扁蒴藤素可通过抑制TGF-β/Smad通路增强ECA109/DDP细胞DDP敏感性。

关键词: 扁蒴藤素, 食管鳞状细胞癌, 顺铂, 化学药物治疗敏感性, 增殖

Abstract: Objective To investigate the mechanism by which pristimerin enhances cis-diamine dichloroplatinum/cisplatin(DDP) sensitivity of esophageal squamous cell carcinoma cell line ECA109. Methods ECA109 cells were treated with 20 μg/mL DDP, with drug concentrations incrementally increased (40, 80, 100 μg/mL) every 2-3 passages. After 3-6 months, stable DDP-resistant ECA109/DDP cells were obtained which proliferated in high DDP concentration environment (80 μg/mL). The ECA109/DDP cells were divided into the following groups: control, DDP (80 μg/mL), pristimerin (1 μmol/L), pristimerin (1 μmol/L)+DDP (80 μg/mL), and pristimerin (1 μmol/L)+DDP (80 μg/mL)+TGF-β activator (SRI-011381) (10 μmol/L). Cell proliferation was assessed by CCK-8 assay and colony formation test; Apoptosis was examined by flow cytometry; Migration and invasion were evaluated via scratch wound healing and Transwell assays, respectively. The protein expressions of multidrug resistance-associated protein 1 (MRP1), P-glycoprotein (P-gp), TGF-β1, Smad4, and CD44 were measured by Western blot. Results Compared with control group, there was no difference in various indicators in the DDP group(P＜0.05). While pristimerin group exhibited a decrease of A₄₅₀ values, colony formation rate, scratch healing rate, number of invasive cells. The protein level of MRP1, P-gp, TGF-β1, Smad4, and CD44 also decreased, along with increased apoptosis (P＜0.05). Compared with the DDP and pristimerin groups, the pristimerin+DDP group showed further reduction in A₄₅₀ values, colony formation rate, scratch healing rate, number of invasive cells, and protein level of MRP1, P-gp, TGF-β1, Smad4, and CD44, as well as increased apoptosis (P＜0.05). Compared with pristimerin+DDP group, pristimerin+DDP+SRI-011381 group showed an opposite trend in all the above indicators (P＜0.05). Conclusions Pristimerin enhances DDP sensitivity in ECA109/DDP cells by inhibition of TGF-β/Smad pathway.

Key words: pristimerin, esophageal squamous cell carcinoma, cisplatin, chemosensitivity, proliferation

中图分类号:

R735.1

刘桂举, 袁威, 吕鼎霖, 韩倩倩, 梅家转, 张浩哲. 扁蒴藤素提高人食管鳞状细胞癌耐药细胞株ECA109/DDP的顺铂敏感性[J]. 基础医学与临床, 2026, 46(9): 1200-1206.

LIU Guiju, YUAN Wei, LYU Dinglin, HAN Qianqian, MEI Jiazhuan, ZHANG Haozhe. Pristimerin sensitizes human esophageal squamous cell carcinoma cell strain ECA109/DDP to cisplatin[J]. Basic & Clinical Medicine, 2026, 46(9): 1200-1206.

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扁蒴藤素提高人食管鳞状细胞癌耐药细胞株ECA109/DDP的顺铂敏感性

Pristimerin sensitizes human esophageal squamous cell carcinoma cell strain ECA109/DDP to cisplatin

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