β-Elemene enhances the efficacy of gefitinib on glioblastoma multiforme cells through the inhibition of the EGFR signaling pathway.

Glioblastoma multiforme (GBM) is the most common and severe form of primary tumor in the central nervous system of adults which has poor prognosis and limited therapeutic options. Epidermal growth factor receptor (EGFR) inhibitor, such as gefitinib (brand name Iressa, ZD1839), has been approved as a targeted medicine for several types of tumor including glioblastoma multiforme. However, gefitinib exerted very limited effects on some glioblastoma multiforme patients after a period of treatment due to intrinsic and acquired drug resistance. β-Elemene, a natural plant drug extracted from Curcuma wenyujin, has shown promising anticancer effects against a broad spectrum of tumors. In the present study, we found that β-elemene could enhance the chemosensitivity of glioblastoma multiforme cells to gefitinib. The combination medication of β-elemene and gefitinib not only inhibited the survival and proliferation of glioblastoma multiforme cells via inhibition of EGFR signaling pathway but also induced more distinct apoptosis and autophagy in the glioblastoma multiforme cells than the gefitinib monotherapy. These results showed that β-elemene might be one potential adjuvant to enhance the effect of EGFR inhibitor and reduce the resistance of gefitinib in glioblastoma multiforme.