Effect of Raddeanin A on the proliferation and apoptosis of cervical cancer HeLa cells through the PI3K/Akt/mTOR signaling pathway

Abstract

Objective To investigate the effect of Raddeanin A （RDA） on the proliferation and apoptosis of cervical cancer HeLa cells and to explore the possible mechanism. Methods HeLa cells were cultured in vitro and treated with RDA at a concentration of 0, 5, 10, 20, and 40 μmol/L for 48 h. Cell proliferation rate was determined by CCK-8. The half-maximal inhibitory concentration （IC50） was calculated to determine the drug concentration. Flow cytometry was used to detect cell apoptosis, and western blot was employed to detect the expression levels of Bcl-2, Bax, Cleaved-caspase-3, p-PI3K, p-Akt, and p-mTOR proteins. Hela cells were divided into four groups： control group, IGF-1 group, RDA group and combined treatment group. The proliferation rate, apoptosis rate, relative expression levels of p-PI3K, p-Akt and p-mTOR proteins were detected and compared among different groups. Results The proliferation rate of HeLa cells was significantly declined, whereas the apoptosis rate was significantly elevated with the increasing concentration of RDA （both P < 0.05）, the relative expression levels of Bax and Cleaved-caspase-3 proteins were significantly up-regulated （both P < 0.05）, whereas those of Bcl-2, p-PI3K, p-Akt and p-mTOR proteins were significantly down-regulated （all P < 0.05）. After the activation of PI3K/Akt/mTOR signaling pathway by IGF-1, RDA could still inhibit the proliferation of HeLa cells and down-regulate the relative expression levels of p-PI3K, p-Akt and p-mTOR proteins （all P < 0.05）. Conclusion RDA can inhibit the proliferation and promote the apoptosis of cervical cancer HeLa cells by suppressing the PI3K/Akt/mTOR signaling pathway.

Keywords

• |raddeanin a|hela cell|cervical cancer|apoptosis|pi3k/akt/mtor signaling pathway