Mechanism of astragaloside-loaded lactosyl chitosan nanoparticles inhibiting MAPK/ERK pathway and preventing angiogenesis and colon cancer development through miR-200.

BACKGROUND

The incidence of colorectal cancer in China continues to rise. Astragaloside IV has been shown to delay its progression and nanoparticles constructed from it with astragaloside-lactosyl chitosan nanoparticles (ALCNPs) exhibit enhanced therapeutic efficacy.

OBJECTIVES

This study aimed to construct novel lactosyl chitosan nanoparticles (ALCNPs) to improve the delivery of astragaloside IV and to investigate its mechanism in inhibiting CRC angiogenesis and progression via the miR-200/MAPK/ERK axis.

METHODS

ALCNPs were prepared using a CRC mouse model and SW480 cells. Evaluations were conducted on proliferation, VEGF expression, MAPK and ERK protein expression, while apoptosis, invasion and MVD count were analyzed to assess angiogenesis.

RESULTS

ALCNPs were successfully prepared, exhibiting spherical morphology with uniform dispersion. They exerted anti-tumor effects by inhibiting angiogenesis and inducing apoptosis in CRC cells through the activation of miR-200. The underlying mechanism involves the downregulation of the MAPK/ERK signaling pathway by miR-200.

CONCLUSION

ALCNPs, as an effective targeted delivery system for Astragaloside IV, can inhibit the MAPK/ERK signaling pathway by upregulating miR-200, thereby suppressing angiogenesis, inducing tumor cell apoptosis and slowing CRC progression.