Tanshinone IIA reverses EGF‑ and TGF‑β1‑mediated epithelial‑mesenchymal transition in HepG2 cells via the PI3K/Akt/ERK signaling pathway

Abstract

Epithelial-to-mesenchymal transition (EMT) is an essential phenotypic conversion involved in cancer progression. Epidermal growth factor (EGF) and transforming growth factor (TGF)-β1 are potent inducers of the EMT. Tanshinone IIA (Tan IIA) is a phenanthrenequinone extracted from the root of Salvia miltiorrhiza Bunge, and its anticancer activity has been demonstrated in numerous studies. However, the mechanisms of action underlying Tan IIA in EGF-and TGF-β1-induced EMT in HepG2 cells remain unknown. Multiple assays were utilized in the present study, including colony formation, wound healing, Transwell invasion, immunofluorescence staining and western blotting, in order to assess the influence of Tan IIA on HepG2 cells induced by 20 ng/ml EGF and 10 ng/ml TGF-β1. The present study reported that Tan IIA treatment decreased EGF-and TGF-β1-enhanced cell colony numbers, migration and invasion, and inhibited EGF-and TGF-β1-induced decreases in the expression levels of E-cadherin, and increases in the expression levels of matrix metalloproteinase-2, N-cadherin, vimentin and Snail. In addition, it was observed that Tan IIA decreased the expression levels of phosphorylated (p)-Akt and p-ERK1/2 induced by EGF and TGF-β1. Furthermore, western blot analysis confirmed that blocking the function of PI3K/Akt and ERK with LY294002 and U0126 resulted in upregulation of E-cadherin expression, and downregulation of vimentin and Snail expression in EGF-and TGF-β1-treated HepG2 cells. In conclusion, to the best of our knowledge, the results of the present study are the first to indicate that Tan IIA may suppress EGF-and TGF-β1-induced EMT in HepG2 cells by deactivating the PI3K/Akt/ERK pathway.

Curcumin attenuates renal interstitial fibrosis of obstructive nephropathy by suppressing epithelial-mesenchymal transition through inhibition of the TLR4/NF-кB and PI3K/AKT signalling pathways

“… 2013 ), and the PI3K/Akt/ERK signalling pathway (Zhang et al. 2019 ). In the present study, the administration of TGF-β1 dramatically promoted the cell viability and EMT, curcumin treatment reversed these affects via the TLR4/NF-κB and the PI3K/AKT pathways, illustrating the mechanism behind curcumin’s anti-EMT activity.…”

Tanshinone IIA Suppresses Proliferation and Inflammatory Cytokine Production of Synovial Fibroblasts from Rheumatoid Arthritis Patients Induced by TNF-α and Attenuates the Inflammatory Response in AIA Mice

“…Tanshinone IIA (Tan IIA) is the main phytochemical isolated from S. miltiorrhiza and is the main contributor to its beneficial cardiovascular effect. Besides, several studies have revealed other medicinal effects of Tan IIA, including anti-tumor, antiproliferation, and anti-inflammatory effects in various cancers, such as non-small-cell lung cancer, liver cancer, cervical cancer, colorectal cancer, and gastric cancer (Sui et al, 2017;Zhang et al, 2018;Liu et al, 2019;Wang R. et al, 2019;Zhang et al, 2019). Additionally, there are also reports that Tan IIA can be used to treat arthritis (Jia et al, 2017;Zhang et al, 2017).…”

<p>Ropivacaine Inhibits the Growth, Migration and Invasion of Gastric Cancer Through Attenuation of WEE1 and PI3K/AKT Signaling via miR-520a-3p</p>

“…For example, Tanshinone IIA (Tan IIA) inhibits EGF and TGF-β1-induced EMT in HepG2 cells by inactivating the PI3K/AKT/ERK pathway. 17 In addition, studies have found that non-SMC condensin I complex subunit G (NCAPG) acts as an oncogene in liver cancer and promotes cell proliferation and reduces apoptosis by activating the PI3K/AKT/FOXO4 pathway. 18 Nevertheless, whether Rop could affect the activation of PI3K/AKT in GC by regulating miR-520a-3p remains unclear.…”