DHA-inhibited proliferation through the PTEN/PI3K/Akt pathway in gastric cancer SGC7901 cells

Objective: This study aims to elucidate the mechanism of anti-proliferation induced by dihydroartemisinin (DHA) on human gastric cancer SGC7901 cells through the PTEN/PI3K/Akt pathway. Methods: SGC7901 cells were treated with DHA at various con- centrations (6.25, 12.5, 25, 50, and 100 μmol/L) in different lengths of time (24, 48, and 72 h). We detected the changes in proliferation through cell count. The cell cycles were measured through flow cytometry. The cells were treated with 100 μmol/L DHAand were cultured for 24 h. The expressions of cyclin D1 and P27 were detected through reverse transcription-polymerase chain reaction and Western blot analysis, respectively. The expressions of PTEN, PI3K, and p-Akt were also detected through Western blot analysis. The PTEN expression was downregulated by the RNAi technology. The cells were subsequently treated with 100 μmol/L DHA for 24 h, followed by a Western blot analysis for the expressions of PTEN, PI3K, p-Akt, cyclin D1, and P27. Results: Results of the cell count showed that DHA greatly inhibited the growth and proliferation of SGC7901 cells in a dose- and time- dependent manner (P<0.05). The DHAinhibited the proliferation of SGC7901 cells through the induced cell cycle G1 phrase arrest. The expressions of cyclin D1, PI3K, and p-Akt were downregulated, and the expressions of P27 and PTEN were upregulated after DHAtreatment (P<0.05). The DHA-elicited decrease in cyclin D1, PI3K, and p-Akt expression was significantly induced, and the DHA-elicited increase in P27 and PTEN expression was significantly reduced (P<0.05) when the SGC7901 cells were transfected with PTEN-specific siRNA to block the endogenous PTEN expression induced by DHA. Conclusion: DHAinduces the cell cycle G0/G1 phase arrest through the regulation of cyclin D1 and P27 expression by activating the PTEN/ PI3K/Akt signaling pathway in human gastric cancer SGC7901 cells.