ABSTRACT
Concurrent radio chemotherapy treatment prolongs the survival rate of patients with advanced cervical cancer; however, it has adverse sideeffects. ßelemene, an active component of the traditional Chinese medicinal herb Curcuma zedoaria, is a promising alternative therapeutic drug for the treatment of advanced cervical cancer. The aim of the present study was to investigate the antitumor effects of ßelemene in human cervical cancer SiHa cells and to determine its underlying therapeutic molecular mechanisms. Cell viability, cell cycle progression and apoptosis were detected using an MTT assay and flow cytometry analysis. Furthermore, the levels of cell migration and cell invasion were investigated using Transwell and wound healing assays. The expression levels of Cyclindependent kinase inhibitor 2B (P15), Cyclin D1, cellular tumor antigen p53, apoptosis regulator Bcl2 (Bcl2), apoptosis regulator BAX (Bax), 72 kDa type IV collagenase (MMP2), matrix metalloproteinase9 (MMP9), ßcatenin, transcription factor 7 (TCF7), and Myc protooncogene protein (cMyc) were analyzed via western blotting. The results revealed that ßelemene inhibited the proliferation of SiHa cells in a dose and timedependent manner. Administration of ßelemene induced G1 phase cellcycle arrest, as demonstrated by the upregulation of P15 expression and the downregulation of Cyclin D1 expression. Furthermore, the present study revealed that ßelemene induced apoptosis in SiHa cells by enhancing the expression of p53 and Bax, and suppressing the expression of Bcl2. In addition, treatment with ßelemene inhibited cell migration and invasion via downregulation of MMP2 and MMP9 expression levels. Western blotting demonstrated that ßelemene reduced the expression levels of ßcatenin and its downstream target molecule TCF7, thus resulting in reduced levels of their target proteins, including cMyc, Cyclin D1, Bax and MMP2 in cervical cancer cells. The results of the present study suggested that ßelemene may inhibit cell proliferation and invasion, in addition to inducing apoptosis, via attenuation of the Wnt/ßcatenin signaling pathway in cervical cancer cells.