Artesunate inhibits proliferation and migration of RPE cells and TGF-ß2 mediated epithelial mesenchymal transition by suppressing PI3K/AKT pathway.

AIM: To study the braking effectiveness of artesunate on transforming growth factor (TGF)-ß2 mediated epithelial-mesenchymal transition (EMT) in retinal pigment epithelium (RPE) in vitro. METHODS: The fostered ARPE-19 cells were processed with artesunate alone or combined with the TGF-ß2. The CCK-8 examination was utilized to test the cell propagation. Cell migration was detected by scratch as well as the Transwell examination. The EMT characters and activation of PI3K/Akt signal channel were estimated by Western blotting and immunofluorescence. The Western blotting was utilized in order to confirm the vitreous of controls as well as patients with proliferative vitreoretinopathy (PVR) were collected and the levels of PI3K, phospho-PI3K, Akt. RESULTS: Disposal of ARPE-19 cells with artesunate (50-150 µmol/L) obviously suppressed their propagation and immigration, which dependent on the concentration and time. Artesunate suppressed the EMT which was induced by TGF-ß2 in ARPE-19 cells through sustaining the expression of vimentin and α-SMA through the suppression of PI3K, phospho-PI3K, phospho-Akt and Akt. Levels of PI3K, phospho-PI3K, AKT and phospho-Akt was increased in the vitreous in PVR (P<0.05). CONCLUSION: Such findings indicate that PI3K/Akt signal channel is highly activated in vitreous of PVR. Artesuante is an operative depressor of the propagation, immigration and TGF-ß2-mediated EMT of ARPE-19 cells by reduced the expression of PI3K/Akt channel.

Artesunate inhibits the development of PVR by suppressing the TGF-ß/Smad signaling pathway.

Proliferative vitreoretinopathy (PVR) is the main cause of retinal detachment surgery failure. The epithelial-mesenchymal transition (EMT) induced by transforming growth factor (TGF-ß2) plays an important role in the development of PVR. Artesunate has been widely studied as a treatment for ophthalmic diseases because of its antioxidant, anti-inflammatory, antiapoptotic and antiproliferative properties. The purpose of this study was to investigate the effects of artesunate on the TGF-ß2-induced EMT in ARPE-19 cells and PVR development. We found that artesunate inhibited the proliferation and contraction of ARPE-19 cells after the EMT and the autocrine effects of TGF-ß2 on ARPE-19 cells. Additionally, the levels of Smad3 and p-Smad3 were increased in clinical samples, and artesunate decreased the levels of Smad3 and p-Smad3 in ARPE-19 cells treated with TGF-ß2. Artesunate also inhibited the occurrence and development of PVR in vivo. In summary, artesunate inhibits the occurrence and development of PVR by inhibiting the EMT in ARPE-19 cells.