The Effects of Pachymic Acid on Colorectal Cancer Cell Proliferation and Metastasis via the MiR-148a-5p/IFI6 Pathway

Abstract

Background: Pachymic acid (PA), a purified triterpene extracted from the medicinal fungus Poria cocos, is known for its antiemetic, anti-inflammatory, and antitumor properties. However, the effect of PA on colorectal cancer and its underlying mechanism are yet to be elucidated. In this study, we delved into the chemotherapeutic effects and underlying mechanisms of PA on colorectal cancer. Methods: The impact of PA on the proliferation of cells in colon cancer was investigated employing the Cell Counting Kit-8 (CCK-8) and 5-ethynyl-2′-deoxyuridine (EdU). Moreover, its role in the migration of colon cancer cells was assessed using the transwell assay. Bioinformatic analysis was performed to predict interferon alpha-inducible protein 6 (IFI6) binding miRNA and dual luciferase assay was used to validate this interaction. The IFI6-overexpressing cell lines were established and used to evaluate if PA regulates IFI6 to affect a serine/threonine protein kinase (AKT) and SMAD Family Member 3 (Smad 3) signaling pathways by western blot between control, PA + Vector and PA + IFI6-overexpression (OE) groups. Furthermore, miR-148a-5p inhibitor was applied to investigate the effect of PA on colorectal cancer cells. Results: PA showed antitumor effects in vitro by inhibiting colon cancer cell proliferation and metastasis in HT29 and DLD-1 cells (p < 0.01). Mechanistically, our data suggested that PA decreased colon cancer cell proliferation and metastasis by increasing miR-148a-5p expression to repress the levels of IFI6, AKT, and Smad 3 signaling pathways (p < 0.05). Moreover, overexpression of IFI6 and administration of miR-148a-5p inhibitors reversed the inhibitory effects of PA on the AKT and Smad-3 pathways (p < 0.01), indicating a critical role for IFI6 in colorectal cancer progression. Conclusion: Our study indicates PA as a potential therapeutic candidate for colorectal cancer growth and metastasis. This study provides a foundation for the potential application of PA in colorectal cancer therapy.