Zhang Congkai, Zhu Chao, Huang Haoxuan, Liu Mengwei, Yu Kuai, Le Aiping
Department of Transfusion Medicine, Key Laboratory of Jiangxi Province for Transfusion Medicine, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University Nanchang, Jiangxi, P. R. China.
Department of Oncology, Jingzhou Hospital Affiliated to Yangtze University Jingzhou, Hubei, P. R. China.
Am J Transl Res. 2025 Aug 15;17(8):6028-6041. doi: 10.62347/VAFF5386. eCollection 2025.
The incidence of gastric cancer (GC) is increasing worldwide, and it ranks among the leading causes of cancer-related mortality. Platinum-based chemotherapeutic agents are commonly employed in the treatment of various solid tumors; however, the development of drug resistance remains a crucial barrier to effective treatment. T cell immunoglobulin and mucin domain 1 (TIM1) has been implicated in the initiation and progression of various tumors. Nevertheless, the influence of TIM1 on the efficacy of platinum-based chemotherapeutics and its biologic implications in GC have not been thoroughly investigated.
This study utilized flow cytometry, cell counting kit-8 assays, and western blot to assess the role of TIM1 in modulating sensitivity to platinum drugs. High-throughput sequencing was employed to elucidate the potential mechanism of TIM1. Additionally, the effect of TIM1 on the biologic characteristics of GC was further investigated through clinical specimens, cells, and animals.
Knockdown of TIM1 enhanced the sensitivity of GC cells to platinum chemotherapeutic drugs. Furthermore, TIM1 expression was elevated in GC tissues, and high TIM1 expression predicted poor survival outcomes in GC patients. Knockdown of TIM1 inhibited the malignant behaviors of GC cells in vitro and in vivo. The mitogen-activated protein kinase (MAPK) signaling pathway may play a role in the regulatory effects of TIM1 on GC cells.
Overall, TIM1 functions as an oncogene in GC. Knockdown of TIM1 enhances platinum chemosensitivity and inhibits malignant behavior in GC through the MAPK signaling pathway. These findings reveal a molecular mechanism contributing to chemotherapy resistance and suggest a therapeutic strategy for enhancing chemotherapy.
全球范围内胃癌（GC）的发病率正在上升，它位列癌症相关死亡的主要原因之一。铂类化疗药物常用于治疗各种实体瘤；然而，耐药性的产生仍然是有效治疗的关键障碍。T细胞免疫球蛋白和粘蛋白结构域1（TIM1）与多种肿瘤的发生和发展有关。然而，TIM1对铂类化疗药物疗效的影响及其在胃癌中的生物学意义尚未得到充分研究。
本研究利用流式细胞术、细胞计数试剂盒-8法和蛋白质印迹法评估TIM1在调节对铂类药物敏感性中的作用。采用高通量测序来阐明TIM1的潜在机制。此外，通过临床标本、细胞和动物进一步研究TIM1对胃癌生物学特性的影响。
敲低TIM1可增强胃癌细胞对铂类化疗药物的敏感性。此外，胃癌组织中TIM1表达升高，高TIM1表达预示着胃癌患者的不良生存结局。敲低TIM1在体外和体内均抑制胃癌细胞的恶性行为。丝裂原活化蛋白激酶（MAPK）信号通路可能在TIM1对胃癌细胞的调节作用中发挥作用。
总体而言，TIM1在胃癌中作为一种癌基因发挥作用。敲低TIM1可增强铂类化疗敏感性，并通过MAPK信号通路抑制胃癌的恶性行为。这些发现揭示了导致化疗耐药的分子机制，并提出了一种增强化疗效果的治疗策略。
