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

被引：38

作者：

Miyata, Haruo ^{[1
]}

Ashizawa, Tadashi ^{[1
]}

Iizuka, Akira ^{[1
]}

Kondou, Ryota ^{[1
]}

Nonomura, Chizu ^{[1
]}

Sugino, Takashi ^{[3
]}

Urakami, Kenichi ^{[2
]}

Asai, Akira ^{[6
]}

Hayashi, Nakamasa ^{[4
]}

Mitsuya, Koichi ^{[4
]}

Nakasu, Yoko ^{[4
]}

Yamaguchi, Ken ^{[5
]}

Akiyama, Yasuto ^{[1
,4
]}

机构：

[1] Shizuoka Canc Ctr Hosp, Div Immunotherapy, 1007 Shimonagakubo,Nagaizumi Cho, Shizuoka 4118777, Japan

[2] Shizuoka Canc Ctr Hosp, Shizuoka Canc Ctr Res Inst, Canc Diagnost Div, Shizuoka, Japan

[3] Shizuoka Canc Ctr Hosp, Div Pathol, Shizuoka, Japan

[4] Shizuoka Canc Ctr Hosp, Div Neurosurg, Shizuoka, Japan

[5] Shizuoka Canc Ctr Hosp, Off President, Shizuoka, Japan

[6] Univ Shizuoka, Grad Sch Pharmaceut Sci, Shizuoka 4228526, Japan

来源：

CANCER GENOMICS & PROTEOMICS | 2017年 / 14卷 / 01期

关键词：

STAT3; inhibitor; mTOR inhibitor; temozolomide resistance; glioblastoma; ANTITUMOR-ACTIVITY; RAPAMYCIN; MUTATIONS; RAS/RAF/MEK/ERK; RADIOTHERAPY; CONCOMITANT; ACTIVATION; EVOLUTION; CANCER; TRIAL;

D O I：

10.21873/cgp.20021

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

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.

引用

页码：83 / 91

页数：9

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