■胶质瘤的特点是高死亡率和耐药性。即使使用常规化疗,胶质母细胞瘤的预后仍然很差。由于有限的生物利用度,许多药物不是最佳有效的。冰片可以提高药物的生物利用度,一种单萜类物质。在这项研究中,我们研究了冰片的效果,一种常用的中药,研究C6神经胶质瘤和U251人神经胶质瘤细胞系的化学敏感性,并阐明其治疗分子靶标。
■使用CCK8和克隆形成测定法检查了冰片在C6和U251细胞中的化学敏感性诱导作用。通过免疫组织化学和蛋白质印迹测定评估了冰片作用的潜在机制。Further,通过透射电子显微镜确定自噬体的数量。最后,在C6原位肿瘤移植后的SD大鼠中评价冰片的化学致敏作用。
■冰片响应替莫唑胺(TMZ)增加C6和U251细胞的细胞毒性。此外,通过透射电子显微镜,西方印迹,和免疫组织化学测试,我们发现冰片联合TMZ能显著增加自噬水平,而缺氧诱导因子-1α(HIF-1α)是冰片增强TMZ细胞毒性作用的候选靶点.冰片增强HIF-1α降解的能力在施用自噬抑制剂后被抵消。在体内,发现冰片治疗可增强TMZ的抗癌作用并延迟肿瘤进展,这种作用与其促进HIF-1α自噬降解的能力密切相关。
■HIF-1α可能是冰片的有效治疗靶点,它可以作为一种化疗增敏药物用于神经胶质瘤的治疗。
UNASSIGNED: Gliomas are characterized by high mortality rates and resistance. Even with conventional chemotherapy the prognosis of glioblastoma remains poor. Many medications are not optimally effective due to limited bioavailability. The bioavailability of medicine can be enhanced by borneol, a monoterpenoid substance. In this study, we investigated the effect of borneol, a commonly used Chinese medicine, on chemosensitivity in C6 glioma and U251 human glioma cell lines and elucidated its therapeutic molecular targets.
UNASSIGNED: The chemosensitivity-inducing effects of borneol in C6 and U251 cells were examined using CCK8 and clonal formation assays. The mechanism underlying the effect of borneol was evaluated through immunohistochemistry and western blotting assays. Further, the number of autophagosomes was determined via transmission electron microscopy. Finally, the chemical sensitization effect of borneol was evaluated in SD rats after C6 orthotopic tumor transplantation.
UNASSIGNED: Borneol increased cytotoxicity in C6 and U251 cells in response to temozolomide (
TMZ). In addition, through transmission electron microscopy, western blotting, and immunohistochemical tests, we found that borneol combined with
TMZ significantly increased the level of autophagy and that hypoxia inducible factor-1(HIF-1α) is a candidate target through which borneol enhances the cytotoxic effect of
TMZ. Borneol\'s ability to enhance HIF-1α degradation was counteracted following the administration of autophagy inhibitors. In vivo, borneol treatment was found to enhance the anticancer effect of
TMZ and delay tumor progression, and this effect was closely related to its ability to promote the autophagic degradation of HIF-1α.
UNASSIGNED: HIF-1α might be a valid therapeutic target of borneol, which can be potentially applied as a chemosensitizing drug used for glioma treatment.