β-elemene combined with temozolomide in treatment of brain glioma

Temozolomide (TMZ) is a widely used chemotherapeutic agent for malignant glioma. beta-Elemene has been reported to have the ability of passing through the blood-brain barrier and reverse multidrug resistance. In the present study, transport of drugs through the in vitro blood-brain barrier (BBB) model also suggested that beta-elemene can assist in TMZ transport to the brain. Plasma and brain pharmacokinetics demonstrated that when beta-elemene is used in combination with TMZ, the metabolic rate of TMZ in plasma is slowed, and mean residence time (MRT) in brain is prolonged. The brain tissue distribution at 1 h indicated that the combination of TMZ and beta-elemene promotes the distribution of beta-elemene in the brain but slightly reduces the distribution of TMZ in the brain. Furthermore the antitumor effect and toxicity in vivo were also investigated. The combination of beta-elemene and TMZ was well tolerated and significantly inhibited tumor growth in glioma xenografts. In summary, the present study indicates a synergistic antitumor effect of beta-elemene and TMZ in glioma.