Guggulsterone enhanced inhibitory effect of temozolomide on glioblastoma cells through pbk/akt pathway / 中国药理学通报

ABSTRACT

Aim To investigate the mechanism of the combination of guggulsterone and temozolomide in inhibiting human glioblastoma cells.Methods Glioblastoma U251 cells were treated with guggulsterone and temozolomide alone or in combination.Cell proliferation was determined by CCK-8.The level of apoptosis was evaluated by Hoechst 33342 staining and flow cytometry.PI3K/Akt pathway activity and the level of apoptosis-associated proteins Bcl-2 and Bax expression were analysed by Western blot.Results Guggulsterone(30 μmol·L-1)significantly enhanced the inhibitory effect of temozolomide(1~400 μmol·L-1)on U251 cells, as compared with temozolomide treatment alone.Guggulsterone(30 μmol·L-1)significantly enhanced the effect of temozolomide(400 μmol·L-1)-induced apoptosis on U251 cells, as compared with temozolomide treatment alone(P<0.01).Furthermore, guggulsterone(30 μmol·L-1)significantly down-regulated the expression of PI3K, p-PI3K p110, p-Akt(Ser473)and Bcl-2, as compared with temozolomide treatment alone.Conclusion Guggulsterone enhances the inhibitory effect of temozolomide on human glioblastoma U251 cells through PI3K/Akt pathway.