Inhibition of Colorectal Cancer Progression by Forsythoside A and Enhanced Anti-PD1 Therapy Through Downregulation of LSD1

Background Colorectal cancer (CRC) is the most prevalent malignant tumor of the digestive system and poses a significant threat to human health and survival. Forsythoside A (FSA) is an active monomeric component of Forsythia suspensa (Thunb.) Vahl, which is widely distributed in China, Korea, Japan, and multiple European countries. However, its biological function and clinical significance in CRC remain largely unknown. Purpose This study aims to explore the biological function and potential clinical value of FSA. Materials and Methods A series of in vivo and in vitro assays were performed to evaluate the effect of FSA on CRC cell proliferation, migration, and colony formation phenotype. Bioinformatics analysis and quantitative real-time polymerase chain reaction (qPCR) were conducted to determine the expression level of histone lysine-specific demethylase 1 (LSD1). Cell transfection and qPCR were performed to investigate the anti-tumor mechanism of FSA. Immunohistochemical staining was performed to assess CD8+ T-cell infiltration in tumor tissue. A subcutaneous tumor model was conducted to assess the potential enhanced effect with programmed cell death-1 antibody (anti-PD1) therapy. Results In vivo and in vitro studies revealed that FSA significantly inhibited CRC cell proliferation, migration, colony formation, and tumorigenicity. The bioinformatics analysis and qPCR results indicated that LSD1 was highly expressed in CRC cells and tissues. The mechanistic study indicated that, by downregulating LSD1, FSA suppressed not only malignant biological behavior but also promoted vital immune cells, CD8+ T-cell infiltration, and synergized with anti-PD1 therapy. Conclusion FSA significantly inhibited CRC progression and could be a promising lead compound for CRC immunotherapy.