Ganoderma Spore Lipids Inhibit Perineural Invasion in Pancreatic Cancer by Downregulating NGF-TrkA Pathway.

Abstract

Perineural invasion (PNI) is an important factor leading to the recurrence of pancreatic cancer (PanCa). The NGF-TrkA pathway is related to PNI progression. Ganoderma spore lipid (GSL) is a drug with anti-cancer properties. In this study, we find out whether GSL can prevent PNI of PanCa by inhibiting NGF-TrkA pathway. In vitro, wound healing assays, transwell-based assays and three-dimensional tumor-nerve cell co-culture system showed that GSL significantly inhibited the migration and invasion capacity of PanCa cells. Inhibiting the NGF-TrkA pathway is considered an effective approach for treating PanCa. We showed that GSL effectively inhibited NGF-TrkA pathway via immunofluorescence assays and western blotting analysis. The supplement of recombinant NGF reversed the GSL inhibitory effect on the migration and invasion of PANC-1. In vivo, a sciatic nerve invasion animal model was constructed using BALB/c mice. GSL significantly suppressed tumor growth and suppressed the expression of TrkA, NGF, and vimentin and upregulated the level of the epithelial marker E-Cadherin. Moreover, GSL reduced the expression of S100 and PGP9.5. These findings suggested that GSL effectively inhibited the PNI of PanCa cells by downregulating the NGF-TrkA pathway, which may provide a new adjuvant for PanCa treatment.