化學治療為目前臨床上常見的癌症治療方式，而化學治療通常會引起一些常見副作用例如噁心、嘔吐、抑制骨髓生成和神經疾病。大部分的副作用皆可被預防或治療，除了化療引起之周邊神經病變(Chemotherapy-induced peripheral neuropathy)。由我們先前高通量藥物篩選結果顯示，Minoxidil在大腦皮質及周邊背根神經節(Dorsal root ganglion)細胞皆具有神經保護效果。因此本論文研究整合小鼠行為模式及神經細胞探討Minoxidil是否可以預防太平洋紫杉醇(Paclitaxel)引起之周邊神經病變。在小鼠疼痛行為模式中，Minoxidil可減緩太平洋紫杉醇造成溫覺遲緩且可改善機械性疼痛。利用電子顯微影像觀察坐骨神經(sciatic nerve)的超微結構及髓鞘完整性評估(G-ratio)，發現事先給予Minoxidil會減少太平洋紫杉醇所造成小神經髓鞘之損傷。利用背根神經節細胞探討Minoxidil其神經保護機制，結果顯示Minoxidil可能透過減緩太平洋紫杉醇引起神經發炎與神經細胞內鈣離子失衡之機制，進而達到保護功效。更重要的是，在小鼠腫瘤模式中，Minoxidil與太平洋紫杉醇合併使用具有協同效果以減緩乳癌及子宮頸癌的生長。此外，定量分析毛髮長度和毛髮生長情形均說明Minoxidil能改善化療後毛髮生長品質。綜合以上結果，Minoxidil是一個有高潛力之神經保護劑以預防太平洋紫杉醇引起周邊神經病變。

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.

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