Sauchinone inhibits the proliferation and immune invasion capacity of colorectal cancer cells through the suppression of PD-L1 and MMP2/MM9.

Abstract

Colorectal cancer (CRC) is one of the most common tumors globally and a leading cause of cancer-related death. In China, CRC is the third most common cancer type. Sauchinone is known to exhibit anti-tumor and anti-inflammatory activity, but its effects on CRC have not been investigated to-date Objective: To investigate the effects of Sauchinone on CRC development and metastasis and its underlying mechanism(s) of action. SW480 and HCT116 cells were treated with a range of concentrations of Sauchinone. Cell proliferation was measured using EDU assays and flow cytometry. Treatment with 50 µM Sauchinone decreased the expression of MMP2 and MMP9 and downregulated PD-L1 expression (PD-1/PD-L1) leading to checkpoint inhibition. Sauchinone treatment also enhanced the cytotoxicity of SW840 and HCT116 cells co-cultured with CD8+ T cells. The overexpression of PD-L1 rescued the anti-proliferative and cytotoxic effects of Sauchinone in both types. We show that Sauchinone suppresses CRC cell growth through the downregulation of MMP2 and MM9 expression and PD-1/PD-L1 mediated checkpoint inhibition. Collectively, these data highlight the promise of Sauchinone as a future anti-CRC therapeutic.