BACKGROUND: Liver cancer poses a significant global health challenge owing to its increasing incidence and associated mortality rates. Traditional Chinese Medicine (TCM) has garnered attention for its potential in oncology, with formulations such as Hua Zheng San Ji Fang (HZSJF) exhibiting antineoplastic effects. HZSJF is clinically employed in China for cancer treatment
however, its molecular mechanisms in liver cancer remain elusive. TYRO3 plays a key role in tumor progression via the ERK signaling pathway, rendering it a potential therapeutic target. However, the effect of HZSJF on TYRO3 expression and its downstream signaling in liver cancer remains unexplored. PURPOSE: This study aimed to investigate the molecular mechanisms through which HZSJF alleviates liver cancer progression, focusing on its regulation of TYRO3 and the ERK signaling pathway. METHODS: TYRO3 expression in liver cancer and para-carcinoma tissues was analyzed using immunohistochemistry, reverse transcription-quantitative PCR, and western blotting. Liver cancer cells were used to investigate HZSJF-regulated pathways. Transcriptome sequencing was used to identify HZSJF-targeted genes. Cell proliferation, apoptosis, invasion, and migration were assessed using EdU, YO-PRO-1/PI staining, and transwell assays. ERK signaling involvement was examined using a specific inhibitor and validated in vivo using subcutaneous nude mouse tumor models. RESULTS: HZSJF significantly inhibited TYRO3 expression and ERK pathway activation, reducing proliferation, invasion, and migration while promoting apoptosis. The ERK inhibitor corroborated the pathway's role in the antitumor effects of HZSJF. HZSJF suppressed tumor growth and TYRO3 expression in vivo. CONCLUSION: HZSJF alleviated liver cancer progression through the ERK signaling pathway by inhibiting TYRO3 expression, presenting a potential therapeutic approach.