Combination of a STAT3 Inhibitor and an mTOR Inhibitor Against a Temozolomide-resistant Glioblastoma Cell Line

• Published in: Cancer genomics & proteomics 2017-01, Vol.14 (1), p.83-91
• Main Authors: Miyata, Haruo, Ashizawa, Tadashi, Iizuka, Akira, Kondou, Ryota, Nonomura, Chizu, Sugino, Takashi, Urakami, Kenichi, Asai, Akira, Hayashi, Nakamasa, Mitsuya, Koichi, Nakasu, Yoko, Yamaguchi, Ken, Akiyama, Yasuto
• Format: Article
• Language: English
• ISSN: 1109-6535; 1790-6245
• DOI: 10.21873/cgp.20021

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 (IC sub(50): 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.