Brucea�javanica seed oil enhances the radiosensitivity of esophageal cancer by inhibiting hypoxia-inducible factor 1α, in�vitro and in�vivo

Abstract

Brucea javanica oil emulsion (BJOE) has been used clinically to treat esophageal cancer combined with radiotherapy for numerous years in China. However, the detailed mechanism remains unclear. Thus, the effects of BJOE on the radiosensitivity of esophageal squamous cell carcinoma (ESCC) were evaluated in vitro and in vivo. The growth inhibitory effects of different BJOE concentrations were determined through an MTT assay. Radiosensitivity was evaluated through focal formation measurements and clone formation assays. The effects of BJOE on radiation-induced apoptosis were examined through flow cytometric analysis. The effects of BJOE on hypoxia-inducible factor 1α (HIF-1α) protein levels in vitro and in vivo were respectively analyzed through western blot analyses and enzyme-linked immunosorbent assays. BJOE significantly inhibited ECA109 cell proliferation in a dose- and time-dependent manner. Pretreatment with 2.5 mg/ml BJOE increased ECA109 radiosensitivity. BJOE in combination with radiation increased the DNA double-strand breaks. Compared with radiation alone, BJOE and radiation significantly increased the apoptotic rate of ECA109 cells. BJOE also decreased the HIF-1α protein levels in vitro and in vivo. The results from the present study demonstrated that BJOE enhanced the radiosensitivity of human ESCC. This finding was associated with the inhibition of HIF-1α expression. Therefore, BJOE may be a potential radiotherapy sensitization drug due to its significant anti-hypoxic activity.