Radiosensitivity of human ovarian cancer cells is enhanced by pseudolaric acid B due to the inhibition of the Ras/Raf/ERK signaling pathway

Exp Ther Med. 2018 Jan;15(1):685-690. doi: 10.3892/etm.2017.5500. Epub 2017 Nov 13.

Abstract

Ovarian cancer has the highest mortality rate among gynecological cancers; the most effective therapy for this cancer is a combination of radiation treatment and chemotherapy. However, radiation resistance is the leading factor associated with treatment failure. The present study aimed to investigate pseudolaric acid B (PAB) as a potential radiosensitizer for the treatment of ovarian cancer. The present study performed MTT and clonogenic assays, and demonstrated that PAB could induce a radiosensitizing effect on SKOV-3 cells. An Annexin V/propidium iodide staining assay revealed that PAB exerted a radiosensitizing effect by inducing SKOV-3 cell apoptosis. In addition, western blot analysis demonstrated that the activity of the Ras/RAF proto-oncogene serine/threonine-protein kinase/extracellular signal-regulated kinase signaling pathway was reduced by combination therapy with PAB and irradiation. In conclusion, the present study establishes PAB as a radiosensitizer, and provides a rational basis for the use of PAB and irradiation as a combination therapy to treat ovarian cancer.

Keywords: Ras-Raf-ERK signaling pathway; apoptosis; irradiation; ovarian cancer; pseudolaric acid B; radioresistance.