Matrine reduces the secretion of exosomal circSLC7A6 from cancer-associated fibroblast to inhibit tumorigenesis of colorectal cancer by regulating CXCR5.

Tumor microenvironment (e.g., stromal cells) has been suggested to be implicated in colorectal cancer (CRC) progression. Of which, cancer-associated fibroblasts (CAFs) are believed as one of the key stromal cells in tumors. Traditionally, matrine was used to treat cancers, including CRC. Unfortunately, little is known about whether matrine inhibited CRC progression via CAFs. In this research, we analyzed cell proliferation, invasion and apoptosis by cell colony formation assay, transwell assay and Annexin V staining, respectively. circSLC7A6 and CXCR5 expression levels were examined by RT-qPCR. Exosomes were analyzed by NanoSight Tracking Analysis and exosome markers were probed by westernblot. In the results, we found that matrine significantly led to inhibited cell proliferation and invasion, and increased apoptosis. Moreover, matrine blocked circSLC7A6 exosome secretion from CAFs. circSLC7A6 acted as promoter for CRC cell proliferation and invasion, whereas as inhibitor for apoptosis. Clinically, circSLC7A6 was upregulated in CRC tumor tissues compared to adjacent normal tissues. In addition, circSLC7A6 was associated with higher overall survival. Eventually, we confirmed that chemokine receptor CXCR5 was a crucial effector for circSLC7A6-modulated tumorigenesis. Here, our data suggest matrine inhibits CRC tumorigenesis through blocking exosomal circSLC7A6 release from CAFs. This finding will provide strong evidence for treating CRC using matrine.