Minoxidil is a potential neuroprotective drg for paclitaxel-induced neuropathy

Abstract

Cancer chemotherapy causes common side effects including nausea vomiting bone marrow suppression and nerve system disorder Most of the side effects can be predicted or prevented except the chemotherapy-induced peripheral neuropathy In our previous high-content drug screening minoxidil showed the potential neuroprotective effects both in the in vitro model of cortical and dorsal root ganglion (DRG) neurons Here we integrate the mouse behavior models with mechanistic cell-based assays to demonstrate that minoxidil could prevent paclitaxel-induced peripheral neuropathy Minoxidil protected mice from thermal insensitivity and alleviated mechanical allodynia in paclitaxel-treated mice The ultrastructure and quantified G-ratio of myelin integrity of sciatic nerve tissues isolated from minoxidil/paclitaxel-treated mice supported the observations in mouse behavioral tests The mechanistic study on DRG neurons suggested that minoxidil suppressed neuroinflammation and remodeled the dysregulation of intracellular calcium homeostasis provoked by paclitaxel More importantly minoxidil showed a synergistic anti-tumor effect with paclitaxel both in tumor xenograft models of cervical and breast cancer In addition the quantitative assays on hair length and hair growth both show that minoxidil significantly improved the hair quality after chemotherapy Taken together minoxidil is a promising drug to prevent paclitaxel-induced neuropathy

Date of Award	2016 Jul 4
Language	English
Supervisor	Meng-Ru Shen (Supervisor)