Eriobotrya japonica leaf extract modulates TGFBR3 to affect PI3K/Akt signaling pathway to inhibit lung cancer metastasis

Background. The active components of Eriobotrya japonica leaves exhibit therapeutic effects against lung cancer. This study aimed to investigate the impact of E. japonica leaf extract (EJLE) on lung cancer cell invasion and metastasis by modulating transforming growth factor-beta receptor III (TGFBR3) and preliminarily explore whether this effect is associated with the tumor-related PI3K/Akt signaling pathway. Methods. Core genes and signaling pathways were screened using network pharmacology and TGFBR3 expression levels in lung cancer cells were analyzed immunohistochemically. The effects of EJLE and TGFBR3 on lung cancer cell migration and invasion were validated using wound-healing and Matrigel Transwell experiments. Pathway-related protein expression was detected using western blot. In addition, a xenotransplantation tumor model in nude mice was used to verify the effects of EJLE and TGFBR3 on tumor growth. Results. TGFBR3 was weakly and highly expressed in A549 and H292 cells, respectively. EJLE upregulates TGFBR3 expression, whereas both EJLE and TGFBR3 inhibit lung cancer cell migration and invasion and suppress pathway-related protein expression. Xenograft tumor experiments demonstrated that both EJLE and TGFBR3 significantly inhibited tumor growth. To conclude, EJLE modulates TGFBR3 expression to suppress p-PI3K and p-Akt expression, partially restoring the metastasis-suppressive function of lung cancer cells with low TGFBR3 expression.