Down-regulation of survivin and hypoxia-inducible factor-1 α by β-elemene enhances the radiosensitivity of lung adenocarcinoma xenograft.

Elemene (1-methyl-1-vinyl-2,4-diisopropenyl-cyclohexane) is a naturally occurring compound that can be isolated from the traditional Chinese medicinal herb Curcuma wenyujin. β-elemene, its active component, has recently been demonstrated to enhance the radiosensitivity of human cancer cell lines in vitro and of one animal tumor in vivo. The underlying mechanism, however, is still unclear. In this study, we demonstrated for the first time that β-elemene significantly improves the radiosensitivity of A549 lung adenocarcinoma xenograft in vivo as measured by tumor regrowth delay experiments. Our results showed that β-elemene, at 45 mg/kg, significantly inhibited radiation-induced expression of survivin and hypoxia-inducible factor (HIF)-1 α proteins. Because HIF-1 α is known to regulate survivin transcription and acts as upstream regulator of survivin, it is possible that β-elemene regulates the transcription of survivin through HIF-1 α. Our study suggests that β-elemene is a promising drug to enhance tumor radioresponse, and survivin and HIF-1 α are novel targets of β-elemene.