期刊
JOURNAL OF CELLULAR PHYSIOLOGY
卷 227, 期 3, 页码 976-993出版社
WILEY
DOI: 10.1002/jcp.22806
关键词
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资金
- National Science Council [NSC99-2628-B-016-014-MY3 NSC100-2314-B-040-001]
- Tri-Service General Hospital [TSGH-C100-047]
- Chung Shan Medical University [G099N0002]
Glioblastoma multiforme (GBM) is the most common and aggressive primary brain tumor. Patients diagnosed with GBM have a poor prognosis, and it has been reported that tumor malignancy and GBM recurrence are promoted by STAT3 signaling. As resveratrol (RV), a polyphenol in grapes, is reported to be a potent and non-toxic cancer-preventive compound, the aim of this study was to investigate the therapeutic effect and molecular mechanisms of RV on GBM-derived radioresistant tumor initiating cells (TIC). Firstly, our results showed that primary GBM-CD133+ TIC presented high tumorigenic and radiochemoresistant properties as well as increased protein levels of phosphorylated STAT3. We consistently observed that treatment with shRNA-STAT3 (sh-STAT3) or AG490, a STAT3 inhibitor, significantly inhibited the cancer stem-like cell properties and radioresistance of GBM-CD133+ in vitro and in vivo. Furthermore, treatment of GBM-CD133+ with 100 mu M RV induced apoptosis and enhanced radiosensitivity by suppressing STAT3 signaling. Microarray results suggested that RV or AG490 inhibited the stemness gene signatures of GBM-CD133+ and facilitated the differentiation of GBM-CD133+ into GBM-CD133- or astrocytoma cells. Finally, xenotransplant experiments indicated that RV or sh-STAT3 therapy could significantly improve the survival rate and synergistically enhance the radiosensitivity of radiation-treated GBM-TIC. In summary, RV can reduce in vivo tumorigenicity and enhance the sensitivity of GBM-TIC to radiotherapies through the STAT3 pathway. J. Cell. Physiol. 227: 976993, 2012. (C) 2011 Wiley Periodicals, Inc.
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