Ginkgol C17:1 inhibits tumor growth by blunting the EGF- PI3K/Akt signaling pathway

Abstract

Ginkgol C17:1 has been shown to inhibit apoptosis and migration of cancer cells, but the underlying mechanisms are not fully elucidated. In this study, we explored whether the inhibitory effects of Ginkgol C17:1 were associated with epidermal growth factor receptor (EGFR) and PI3K/Akt signaling. The results showed that EGF treatment increased the phosphorylation of EGFR, PI3K, Akt, mTOR and NF-kB, and also enhanced the proliferation, migration and invasion of HepG2 cells. Ginkgol C17:1 dose-dependently inhibited EGF-induced phosphorylation/activation of all the key components including EGFR, PI3K, Akt, mTOR and NF-kB, leading to a significant reduction either of proliferation or migration and invasion of HepG2 cells. Notably, treatment with Ginkgol C17:1 in mice suppressed the growth of tumor massin vivo, and expression of EGFR in the tumor tissue. The results suggest that Ginkgol C17:1 is a potent tumor inhibiting compound that acts on EGF-induced signal transduction of the PI3K/Akt signaling pathways, and may represent a clinically interesting candidate for cancer therapy.

Fig.1

Ginkgol C17:1 inhibits EGF-induced phosphorylation of EGFR in HepG2 cells.

Fig.2

Ginkgol C17:1 inhibits EGF-induced PI3k/Akt signaling activities.

Fig.3

Ginkgol C17:1 inhibits EGF-induced cell proliferation, migration and invasion.

Fig.4

The size of tumor mass and the immunestaining of EGFR inside the tumor tissue.