AstragalosideIV inhibits the invasion and metastasis of SiHa cervical cancer cells via the TGF‑β1‑mediated PI3K and MAPK pathways.

Abstract

Astragaloside IV is the main ingredient of the medicinal herb Radix astragali, which has reported to have antitumor activity in vitro and in vivo. To determine whether the inhibitory effect of astragaloside IV on the invasion and metastasis of the cervical cancer cells is associated with epithelial‑mesenchymal transition (EMT), wound healing and Transwell assays were performed using SiHa cervical cancer cells and demonstrated that astragaloside IV inhibited invasion and migration of human SiHa cervical cancer cells in vitro. Immunocytochemical and western blot analyses indicated that astragaloside IV inhibited EMT by affecting the expression of transforming growth factor‑β1 (TGF‑β1) and E‑cadherin in the cancer cells. Two Smad‑independent pathways mediated by TGF‑β1 were identified to be associated with the effects of astragaloside IV, namely, mitogen‑activated protein kinase (MAPK) and phosphatidylinositol 3 kinase (PI3K) signaling pathways. The data indicated that astragaloside IV has inhibitory effects on phosphorylation of P38 MAPK, PI3K, AKT and mTOR of SiHa cells of cervical cancer. Furthermore, MAPK and PI3K pathway inhibitors were administered to the cancer cells and the expression of E‑cadherin, a marker of EMT, was determined by reverse transcription‑quantitative polymerase chain reaction. The results demonstrated that MAPK and PI3K pathways were involved in the inhibitory effect of astragaloside IV on EMT. In vivo small animal imaging techniques was performed and demonstrated that astragaloside IV inhibited the metastasis of cervical cancer cells. Taken together, the findings demonstrated that astragaloside IV inhibits the invasion and migration of cervical cancer cells in vitro and in vivo.