Chlorogenic acid exhibits antitumor effect in patient-derived xenograft models and hydrogel-embedded tissue culture drug susceptibility test of tongue cancer

Chlorogenic acid (CGA) is one of the effective components of Chinese medicine plant such as honeysuckle and Eucommia ulmoides. CGA can inhibits various cancer types, but its effectivity against tongue cancer remains unknown. In the present study, we utilized patient-derived xenograft (PDX) models in conjunction with hydrogel-embedded drug sensitivity tests (HDST) to demonstrate the inhibitory effects of CGA on tongue cancer tissues in both in vivo and ex vivo experimental paradigms. Immunohistochemical (IHC) analysis and TUNEL staining revealed that CGA downregulated the expression of CD31 and Ki-67, while concurrently promoting apoptosis. Furthermore, the involvement of the EGFR-AKT-MMP9 signaling cascade in the tumor-suppressive effects of CGA was confirmed using network pharmacology analysis and immunofluorescent validation techniques. Overall, our findings indicate that CGA robustly inhibits tongue cancer in cellular and organismal models. The EGFR-AKT-MMP9 axis plays a highly significant role in mediating this bioactivity, thereby positioning CGA as a promising candidate for further investigation in oncology. The multifaceted therapeutic potential of CGA, as evidenced by its ability to disrupt angiogenesis, suppress cell proliferation, and induce apoptosis, underscores its value as a novel therapeutic agent for the treatment of tongue cancer.