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

Introduction: Paclitaxel (PTX) cannot effectively treat glioma because it cannot cross the bloodbrain 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. Methods: 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 KaplanMeier method, brain tumour pathology and size was observed by HE staining, and in vivo imaging system respectively. Results: 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. Conclusion: 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.