Matrine exerts antitumor activity in cervical cancer by protective autophagy via the Akt/mTOR pathway in vitro and in vivo.

Abstract

Matrine is a quinazoline alkaloid extracted from Sophora flavescens. The aim of the present study was to determine whether matrine can induce autophagy in the human HeLa and SiHa cervical cancer cell lines in vitro and in vivo. Cell viability assay was used to assess the suppressive effect of matrine and cisplatin on the proliferation of HeLa and SiHa cells. A total of 28 4-week-old female BALB/c nude mice were used for the in vivo study. Autophagy and protein expression were observed via transmission electron microscopy, monodansylcadaverine and immunohistochemical staining and western blotting. The inhibitory effect of matrine on the proliferation of cervical cancer cells was time- and dose-dependent. The combination of matrine and cisplatin synergistically inhibited the proliferation of cervical cancer cells in vitro and in vivo. Transmission electron microscopy showed that after the addition of matrine, numerous autophagosomes and autophagolysosomes were observable in HeLa and SiHa cells, as demonstrated by monodansylcadaverine staining. Western blotting and immunohistochemical staining showed that as the concentration of matrine increased, the expression of the autophagy marker LC3A/B-II also increased significantly in vitro and in vivo. These findings suggested that matrine inhibited the proliferation of cervical cancer cells and induced autophagy by inhibiting the Akt/mTOR signaling pathway. Thus, matrine may represented a potential candidate in combination therapy for cervical cancer as an inducer of autophagy.