Phillyrin from Forsythia suspensa suppresses the proliferation, angiogenesis, and metastasis of colorectal cancer via targeting CD147.

ETHNOPHARMACOLOGICAL RELEVANCE: Forsythia suspensa (Thunb.) Vahl, a traditional Chinese herbal medicine, is widely used in clinical practice. Phillyrin (PHN), a major bioactive component of Forsythia suspensa, exhibits significant anti-inflammatory, neuroprotective, and antibacterial properties, offering potential for colorectal cancer (CRC) prevention and treatment.

AIM OF THE STUDY: This study aimed to clarify the effects of PHN on CRC progression, focusing on epithelial-mesenchymal transition (EMT) and angiogenesis, to elucidate the underlying molecular mechanisms involving CD147.

MATERIALS AND

METHODS

In vitro, cell viability and colony formation were conducted to detect the inhibition of PHN on CRC cells. Wound healing and Transwell assays were used to detect the migration and invasion. PCR, Western blot and ELISA were performed to clarify the relevant molecular levels. Overexpression plasmids were constructed to regulate the target molecule for mechanism research. In vivo, subcutaneous xenograft and lung metastasis models evaluated PHN's anti-cancer effects including histological and immunohistochemical (IHC) analysis.

RESULTS

PHN inhibited CRC cell proliferation, migration, and invasion in vitro, downregulating CD147 expression, while CD147 overexpression reversed the effects of PHN. In vivo, PHN significantly suppressed tumor growth and lung metastasis, reducing VEGFA, N-Cadherin, Snail1, and MMP-9 expression, and increasing E-Cadherin levels.

CONCLUSION

These findings indicated that PHN suppressed the proliferation and metastasis of CRC via regulating CD147-mediated EMT and angiogenesis. PHN may be a promising therapeutic agent for CRC treatment in clinic, and CD147 may be a potential target for drug development.