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

doi:10.16352/j.issn.1001-6325.2026.09.1200

Abstract

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

CLC Number:

R735.1

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.

References

[1] 史铁伟, 李天柱, 周静, 等. 5-脂氧合酶激活蛋白抑制剂MK886对人食管癌细胞系增殖和凋亡的影响[J]. 基础医学与临床, 2022, 42:56-61.
[2] Rai V, Abdo J, Agrawal DK. Biomarkers for early detection, prognosis, and therapeutics of esophageal cancers[J]. Int J Mol Sci, 2023, 24:3316. doi: 10.3390/ijms24043316.
[3] Huang P, Sun LY, Zhang YQ. A hopeful natural product, pristimerin, induces apoptosis, cell cycle arrest, and autophagy in esophageal cancer cells[J]. Anal Cell Pathol (Amst), 2019, 2019:6127169. doi: 10.1155/2019/6127169.
[4] Wang L, Lang B, Zhou Y, et al. Up-regulation of miR-663a inhibits the cancer stem cell-like properties of glioma via repressing the KDM2A-mediated TGF-β/SMAD signaling pathway[J]. Cell Cycle, 2021, 20:1935-1952.
[5] 李朝慧, 任本洪, 孙雪娇, 等. 顺铂耐药对食管癌细胞增殖、凋亡、迁移和血管生成的影响[J]. 中国病理生理杂志, 2017, 33:1-6.
[6] 于彬, 于勇, 时磊, 等. 扁蒴藤素对肝细胞癌细胞生物学行为及吉西他滨化疗敏感性的影响[J]. 中国普通外科杂志, 2023, 32: 221-230.
[7] 杜鹃, 刘媛, 杨倩, 等. 牛磺熊去氧胆酸通过TGF-β1/Smad3信号通路对高糖诱导的人脐静脉内皮细胞损伤的影响[J]. 贵州医科大学学报, 2025, 50:875-882.
[8] Wang Y, Feng W, Wang X, et al. The multifaceted mechanisms of pristimerin in the treatment of tumors state-of-the-art[J]. Biomed Pharmacother, 2022, 154:113575. doi: 10.1016/j.biopha.2022.113575.
[9] Feng M, Zhang A, Wu J, et al. Pristimerin induces noxa-dependent apoptosis by activating the FoxO3a pathway in esophageal squamous cell carcinoma[J]. Chin J Nat Med, 2025, 23:585-592.
[10] Li Y, Zhou Z, Qu J, et al. Role of microRNA-4739 in enhancing cisplatin chemosensitivity by negative regulation of RHBDD2 in human cervical cancer cells[J]. Cell Mol Biol Lett, 2024, 29:20. doi: 10.1186/s11658-024-00532-6.
[11] Jin S, Wang W, Xu X, et al. miR-34b-3p-mediated regulation of STC2 and FN1 enhances chemosensitivity and inhibits proliferation in cervical cancer[J]. Acta Biochim Biophys Sin (Shanghai), 2024, 56:740-752.
[12] Yu D, Shin HS, Lee YS, et al. miR-106b modulates cancer stem cell characteristics through TGF-β/Smad signaling in CD44-positive gastric cancer cells[J]. Lab Invest, 2014, 94:1370-1381.

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