Zhang Xiaomin, Chen Yidan, Yao Ju, Zhang Yingxin, Li Mengying, Yu Bo, Wang Kaifeng
Hangzhou Push-Kang Biotechnology Co., Ltd., Hangzhou, 310030, Zhejiang, PR China.
Cancer Research Institution, Hangzhou Cancer Hospital, Hangzhou, 310002, Zhejiang, PR China.
Biochem Biophys Rep. 2021 Sep 28;28:101144. doi: 10.1016/j.bbrep.2021.101144. eCollection 2021 Dec.
Temozolomide (TMZ) is a widely used chemotherapeutic agent for malignant glioma. β-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 β-elemene can assist in TMZ transport to the brain. Plasma and brain pharmacokinetics demonstrated that when β-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 β-elemene promotes the distribution of β-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 β-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 β-elemene and TMZ in glioma.
替莫唑胺(TMZ)是一种广泛用于治疗恶性胶质瘤的化疗药物。据报道,β-榄香烯具有穿过血脑屏障和逆转多药耐药性的能力。在本研究中,药物通过体外血脑屏障(BBB)模型的转运也表明,β-榄香烯可以协助TMZ转运至脑部。血浆和脑药代动力学表明,当β-榄香烯与TMZ联合使用时,TMZ在血浆中的代谢速率减慢,在脑中的平均驻留时间(MRT)延长。1小时时的脑组织分布表明,TMZ与β-榄香烯联合使用可促进β-榄香烯在脑中的分布,但会略微降低TMZ在脑中的分布。此外,还研究了其体内抗肿瘤作用和毒性。β-榄香烯与TMZ联合使用耐受性良好,可显著抑制胶质瘤异种移植物中的肿瘤生长。总之,本研究表明β-榄香烯与TMZ在胶质瘤中具有协同抗肿瘤作用。