Anti-glioma effect of paclitaxel mediated by specific mode electroacupuncture stimulation and the related role of the Hedgehog pathway

• Published in: Brain research bulletin 2024-07, Vol.213, p.110985, Article 110985
• Main Authors: Ma, Congcong, Ye, Qinyu, Qian, Kecheng, Dai, Mengyuan, Gan, Lin, Yang, Jinding, Jia, Zhaoxing, Pan, Zixin, Cai, Qian, Jiang, Tianxiang, Lin, Xianming
• Format: Article
• Language: English
• Subjects: Animals; Antineoplastic Agents, Phytogenic - pharmacology; Blood brain barrier; Blood-Brain Barrier - drug effects; Blood-Brain Barrier - metabolism; Brain - drug effects; Brain - metabolism; Brain Neoplasms - metabolism; Brain Neoplasms - therapy; Cell Line, Tumor; Electroacupuncture - methods; Glioma; Glioma - metabolism; Glioma - therapy; Hedgehog pathway; Hedgehog Proteins - metabolism; Male; Paclitaxel; Paclitaxel - pharmacology; Rats; Rats, Sprague-Dawley; Signal Transduction - drug effects; Signal Transduction - physiology; Specific mode electroacupuncture stimulation
• ISSN: 0361-9230; 1873-2747; 1873-2747
• DOI: 10.1016/j.brainresbull.2024.110985

Paclitaxel (PTX) cannot effectively treat glioma because it cannot cross the bloodbrain barrier (BBB). A specific mode electroacupuncture stimulation (SMES) can temporarily open the BBB, thereby improving drug delivery to the brain. This study aimed to observe SMES-mediated accumulation of PTX in the brain and its anti-glioma effect and explore the role of the Hedgehog pathway. The acupoint selectivity of SMES in opening the BBB was examined in normal rats. The penetration and anti-glioma activity were determined in a C6-Luc glioma rat model. SMES was performed using 2/100 Hz, 3 mA, 6–6 s, and 40 min The survival curve was analysed by the KaplanMeier method, brain tumour pathology and size was observed by HE staining, and in vivo imaging system respectively. SMES-induced BBB opening had acupoint selectivity. SMES could improve PTX accumulation in brain and SMES-mediated PTX delivery showed enhanced anti-glioma activity due to better brain penetration. Hedgehog pathway was involved in SMES-mediated PTX delivery by regulating Occludin expression. SMES at the head acupoints to deliver PTX is a feasible and effective method for treating glioma. The Hedgehog pathway may play a key role in SMES-mediated PTX delivery across the BBB. [Display omitted] •SMES intervention can open the BBB at the stimulation point of the head, but not the limbs and trunk.•SMES increased the accumulation of PTX in different regions of the glioma brain.•Paclitaxel exerted anti-glioma effect when it reaches a sufficient concentration in the brain.•The Hedgehog pathway participates in the mechanism of SMES open BBB.