期刊
INTERNATIONAL JOURNAL OF NANOMEDICINE
卷 10, 期 -, 页码 7345-7358出版社
DOVE MEDICAL PRESS LTD
DOI: 10.2147/IJN.S93758
关键词
thermoresistance; CD90(+) LCSCs; magnetic hyperthermia; 17-AAG
资金
- National Key Basic Research Program of China (973 Program) [2013 CB933904, 2011CB933500]
- National Natural Science Foundation of China [81271635, 81301270, 81201131]
- National Natural Science Foundation of Jiangsu Province [BK2012335]
- Fundamental Research Funds for the Central Universities
- Regular University Graduate Student Scientific Research Innovation Projects of Jiangsu Province [KYLX_0204]
- Scientific Research Foundation of the Graduate School of Southeast University
- Southeast University Excellent Doctor Degree Thesis Training Fund [YBJJ1459]
Purpose: To explore the thermoresistance and expression of heat-shock protein 90 (HSP90) in magnetic hyperthermia-treated human liver cancer stem-like cells (LCSCs) and the effects of a heat-shock protein HSP90 inhibitor 17-allylamino-17-demethoxgeldanamycin (17-AAG) on hepatocellular carcinoma-burdened nude mice. Methods: CD90(+) LCSCs were isolated by magnetic-activated cell sorting from BEL-7404. Spheroid formation, proliferation, differentiation, drug resistance, and tumor formation assays were performed to identify stem cell characteristics. CD90-targeted thermosensitive magnetoliposomes (TMs)-encapsulated 17-AAG (CD90@17-AAG/TMs) was prepared by reverse-phase evaporation and its characteristics were studied. Heat tolerance in CD90+ LCSCs and the effect of CD90@ 17-AAG/TMs-mediated heat sensitivity were examined in vitro and in vivo. Results: CD90(+) LCSCs showed significant stem cell-like properties. The 17-AAG/TMs were successfully prepared and were spherical in shape with an average size of 128.9 +/- 7.7 nm. When exposed to magnetic hyperthermia, HSP90 was up-regulated in CD90(+) LCSCs. CD90@ 17AAG/TMs inhibited the activity of HSP90 and increased the sensitivity of CD90+ LCSCs to magnetic hyperthermia. Conclusion: The inhibition of HSP90 could sensitize CD90(+) LCSCs to magnetic hyperthermia and enhance its anti-tumor effects in vitro and in vivo.
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