Knockdown of TIM1 enhances platinum chemosensitivity and inhibits progression through the MAPK signaling pathway in gastric cancer.

OBJECTIVES

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.

METHODS

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.

RESULTS

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.

CONCLUSIONS

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.