STAT3 Inhibitor ODZ10117 Suppresses Glioblastoma Malignancy and Prolongs Survival in a Glioblastoma Xenograft Model

被引：32

作者：

Kim, Byung-Hak ^{[1
,2
,3
]}

Lee, Haeri ^{[1
,2
]}

Park, Cheol Gyu ^{[4
]}

Jeong, Ae Jin ^{[1
,2
]}

Lee, Song-Hee ^{[1
,2
]}

Noh, Kum Hee ^{[1
,2
]}

Park, Jong Bae ^{[5
]}

Lee, Chung-Gi ^{[3
]}

Paek, Sun Ha ^{[6
,7
,8
]}

Kim, Hyunggee ^{[4
]}

Ye, Sang-Kyu ^{[1
,2
,8
,9
]}

机构：

[1] Seoul Natl Univ, Dept Pharmacol, Coll Med, Seoul 03080, South Korea

[2] Seoul Natl Univ, Coll Med, Biomed Sci Project BK21PLUS, Seoul 03080, South Korea

[3] CYTUS H&B Corp, Cheongju 28159, South Korea

[4] Korea Univ, Sch Life Sci & Biotechnol, Dept Biotechnol, Seoul 02841, South Korea

[5] Natl Canc Ctr, Grad Sch Canc Sci & Policy, Dept Syst Canc Sci, Goyang 10408, South Korea

[6] Seoul Natl Univ, Dept Neurosurg, Coll Med, Seoul 03080, South Korea

[7] Seoul Natl Univ, Canc Res Inst, Coll Med, Seoul 03080, South Korea

[8] Seoul Natl Univ, Ischem Hypox Dis Inst, Coll Med, Seoul 03080, South Korea

[9] Seoul Natl Univ, Neuroimmune Informat Storage Network Res Ctr, Coll Med, Seoul 03080, South Korea

来源：

CELLS | 2020年 / 9卷 / 03期

基金：

新加坡国家研究基金会;

关键词：

glioblastoma; glioma stem cell (GSC); ODZ10117; STAT3; targeted therapy; TUMOR-INITIATING CELLS; GLIOMA STEM-CELLS; SIGNAL TRANSDUCER; CANCER; IDENTIFICATION; ACTIVATION; TARGET;

D O I：

10.3390/cells9030722

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

Constitutively activated STAT3 plays an essential role in the initiation, progression, maintenance, malignancy, and drug resistance of cancer, including glioblastoma, suggesting that STAT3 is a potential therapeutic target for cancer therapy. We recently identified ODZ10117 as a small molecule inhibitor of STAT3 and suggested that it may have an effective therapeutic utility for the STAT3-targeted cancer therapy. Here, we demonstrated the therapeutic efficacy of ODZ10117 in glioblastoma by targeting STAT3. ODZ10117 inhibited migration and invasion and induced apoptotic cell death by targeting STAT3 in glioblastoma cells and patient-derived primary glioblastoma cells. In addition, ODZ10117 suppressed stem cell properties in glioma stem cells (GSCs). Finally, the administration of ODZ10117 showed significant therapeutic efficacy in mouse xenograft models of GSCs and glioblastoma cells. Collectively, ODZ10117 is a promising therapeutic candidate for glioblastoma by targeting STAT3.

引用

页数：16

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