Spinosyn A and Its Derivative Inhibit Colorectal Cancer Cell Growth via the EGFR Pathway

Area of Science:

• Oncology
• Pharmacology
• Molecular Biology

Background:

• Spinosyn A (SPA) and its derivative LM2I, derived from Saccharopolyspora spinosa, exhibit potential anticancer properties.
• The precise mechanisms by which SPA and LM2I inhibit human colorectal cancer (CRC) cell growth remain largely unelucidated.

Purpose of the Study:

• To investigate the antiproliferative effects of SPA and LM2I on human colorectal cancer cells.
• To elucidate the molecular mechanisms underlying the observed inhibitory effects, focusing on differentially expressed genes and signaling pathways.

Main Methods:

• Cell viability was assessed using MTT and colony formation assays across seven CRC cell lines.
• Bioinformatic analyses, including Gene Ontology (GO), KEGG pathway analysis, and protein-protein interaction (PPI) networks, were employed on gene expression datasets (GSE2509, GSE10843).
• The identified hub gene was validated using Western blot and CRISPR/Cas9 gene editing.

Main Results:

• SPA and LM2I demonstrated significant antiproliferative activity in vitro across seven colorectal cancer cell lines and in vivo in colorectal xenograft models.
• Bioinformatic analysis identified 69 differentially expressed genes (DEGs) between sensitive and insensitive cell lines.
• Epidermal growth factor receptor (EGFR) was identified as the key hub gene, and its pathway was found to be inhibited by SPA and LM2I both in vitro and in vivo.

Conclusions:

• SPA and LM2I possess significant therapeutic potential against colorectal cancer.
• The antiproliferative effects of SPA and LM2I are mediated, at least in part, through the inhibition of the EGFR signaling pathway.
• EGFR is a critical molecular target for the action of SPA and LM2I in colorectal cancer treatment.