Overcoming chemo/radio-resistance of pancreatic cancer by inhibiting STAT3 signaling
dc.contributor.author | Wu, Xiaoqing | |
dc.contributor.author | Tang, Wenhua | |
dc.contributor.author | Marquez, Rebecca T. | |
dc.contributor.author | Li, Ke | |
dc.contributor.author | Highfill, Chad Allen | |
dc.contributor.author | He, Fengtian | |
dc.contributor.author | Lian, Jiqin | |
dc.contributor.author | Lin, Jiayuh | |
dc.contributor.author | Fuchs, James R. | |
dc.contributor.author | Ji, Min | |
dc.contributor.author | Li, Ling | |
dc.contributor.author | Xu, Liang | |
dc.date.accessioned | 2017-09-22T17:24:57Z | |
dc.date.available | 2017-09-22T17:24:57Z | |
dc.date.issued | 2016-02-12 | |
dc.identifier.citation | Wu, X., Tang, W., Marquez, R. T., Li, K., Highfill, C. A., He, F., … Xu, L. (2016). Overcoming chemo/radio-resistance of pancreatic cancer by inhibiting STAT3 signaling. Oncotarget, 7(10), 11708–11723. http://doi.org/10.18632/oncotarget.7336 | en_US |
dc.identifier.uri | http://hdl.handle.net/1808/25000 | |
dc.description.abstract | Chemo/radio-therapy resistance to the deadly pancreatic cancer is mainly due to the failure to kill pancreatic cancer stem cells (CSCs). Signal transducer and activator of transcription 3 (STAT3) is activated in pancreatic CSCs and, therefore, may be a valid target for overcoming therapeutic resistance. Here we investigated the potential of STAT3 inhibition in sensitizing pancreatic cancer to chemo/radio-therapy. We found that the levels of nuclear pSTAT3 in pancreatic cancer correlated with advanced tumor grade and poor patient outcome. Liposomal delivery of a STAT3 inhibitor FLLL32 (Lip-FLLL32) inhibited STAT3 phosphorylation and STAT3 target genes in pancreatic cancer cells and tumors. Consequently, Lip-FLLL32 suppressed pancreatic cancer cell growth, and exhibited synergetic effects with gemcitabine and radiation treatment in vitro and in vivo. Furthermore, Lip-FLLL32 reduced ALDH1-positive CSC population and modulated several potential stem cell markers. These results demonstrate that Lip-FLLL32 suppresses pancreatic tumor growth and sensitizes pancreatic cancer cells to radiotherapy through inhibition of CSCs in a STAT3-dependent manner. By targeting pancreatic CSCs, Lip-FLLL32 provides a novel strategy for pancreatic cancer therapy via overcoming radioresistance. | en_US |
dc.publisher | Impact Journals | en_US |
dc.rights | This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. | en_US |
dc.rights.uri | https://creativecommons.org/licenses/by/4.0/ | en_US |
dc.subject | Chemo/radio-resistance | en_US |
dc.subject | pSTAT3 | en_US |
dc.subject | Pancreatic cancer | en_US |
dc.subject | lip-FLLL32 | en_US |
dc.subject | CSCs | en_US |
dc.title | Overcoming chemo/radio-resistance of pancreatic cancer by inhibiting STAT3 signaling | en_US |
dc.title.alternative | Overcoming chemo/radio-resistance of pancreatic cancer by inhibiting STAT3 signaling | en_US |
dc.type | Article | en_US |
kusw.kuauthor | Wu, Xiaoqing | |
kusw.kuauthor | Tang, Wenhua | |
kusw.kuauthor | Marquez, Rebecca T. | |
kusw.kuauthor | Li, Ke | |
kusw.kuauthor | Highfill, Chad A. | |
kusw.kuauthor | He, Fengtian | |
kusw.kuauthor | Xu, Liang | |
kusw.kudepartment | Molecular Biosciences and Radiation Oncology | en_US |
dc.identifier.doi | 10.18632/oncotarget.7336 | en_US |
kusw.oaversion | Scholarly/refereed, publisher version | en_US |
kusw.oapolicy | This item meets KU Open Access policy criteria. | en_US |
dc.identifier.pmid | PMC4905505 | en_US |
dc.rights.accessrights | openAccess |
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