Combination of a STAT3 Inhibitor and an mTOR Inhibitor Against a Temozolomide-resistant Glioblastoma Cell Line
Combination of a STAT3 Inhibitor and an mTOR Inhibitor Against a Temozolomide-resistant Glioblastoma Cell Line
复制标题
DOI：
10.21873/cgp.20021
复制
发表时间：
2017-01-01
影响因子：
2.5
通讯作者：
Akiyama, Yasuto
中科院分区：
文献类型：
--
作者：
Miyata, Haruo;Ashizawa, Tadashi;Akiyama, Yasuto
TMZ-R背景：替莫唑胺耐药(TMZ-R)胶质母细胞瘤治疗非常困难，需要一种新的方法来克服耐药性。材料和方法：研究STAT3抑制剂STX-0119与雷帕霉素联合作用于我们已建立的TMZ耐药U87细胞株的效果。结果：联合用药对TMZ-R U87细胞有明显的生长抑制作用(IC50：STX-0119为78 mU M，雷帕霉素为30.5 mU M，两者合用为11.3 mU M)。Western blotting分析表明，除雷帕霉素抑制mTOR通路外，STX-0119还通过调节YKL-40的表达抑制S6和4E-BP1的激活。结论：STAT3通路与YKL-40蛋白介导的mTOR下游通路有关，联合应用STAT3抑制剂和雷帕霉素可作为治疗TMZ耐药复发胶质瘤的新途径。
TMZ-R Background: Temozolomide-resistant (TMZ-R) glioblastoma is very difficult to treat, and a novel approach to overcome resistance is needed. Materials and Methods: The efficacy of a combination treatment of STAT3 inhibitor, STX-0119, with rapamycin was investigated against our established TMZ-resistant U87 cell line. Results: The growth-inhibitory effect of the combination treatment was significant against the TMZ-R U87 cell line (IC50: 78 mu M for STX-0119, 30.5 mu M for rapamycin and 11.3 mu M for combination of the two). Western blotting analysis demonstrated that the inhibitory effect of STX-0119 on S6 and 4E-BP1 activation through regulation of YKL-40 expression occurred in addition to the inhibitory effect of rapamycin against the mTOR pathway. Conclusion: These results suggest that the STAT3 pathway is associated with the mTOR downstream pathway mediated by YKL-40 protein, and the combination therapy of the STAT3 inhibitor and rapamycin could be worth developing as a novel therapeutic approach against TMZ-resistant relapsed gliomas.