期刊
ONCOLOGY REPORTS
卷 35, 期 1, 页码 343-351出版社
SPANDIDOS PUBL LTD
DOI: 10.3892/or.2015.4346
关键词
glioblastoma-initiating cells; resveratrol; temozolomide; chemoresistance; combination
类别
资金
- National Natural Science Foundation of China [81102463]
- China National Clinical Research Center for Neurological Diseases
- Training Plan for Beijing High-Level Healthcare Personnel [2011-3-28]
- Capital Medical University Clinical-Basic Cooperation Research [11JL16]
Glioblastoma-initiating cells play crucial roles in the origin, growth, and recurrence of glioblastoma multi-forme. The elimination of glioblastoma-initiating cells is believed to be a key strategy for achieving long-term survival of glioblastoma patients due to the highly resistant property of glioblastoma-initiating cells to temozolomide. Resveratrol, a naturally occurring polyphenol, has been widely studied as a promising candidate for cancer prevention and treatment. Whether resveratrol could enhance the sensitivity of glioblastoma-initiating cells to temozolomide therapy has not yet been reported. Here, using patient-derived glioblastoma-initiating cell lines, we found that resveratrol sensitized glioblastoma-initiating cells to temozolomide both in vitro and in vivo. Furthermore, we showed that resveratrol enhanced glioblastoma-initiating cells to temozolomide-induced apoptosis through DNA double-stranded breaks/pATM/pATR/p53 pathway activation, and promoted glioblastoma-initiating cell differentiation involving p-STAT3 inactivation. Our results propose that temozolomide and resveratrol combination strategy may be effective in the management of glioblastoma patients, particularly for those patients who have been present with a high abundance of glioblastoma-initiating cells in their tumors and show slight responsiveness to temozolomide.
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