https://scholars.lib.ntu.edu.tw/handle/123456789/606148
Title: | Chloroquine potentiates the anticancer effect of pterostilbene on pancreatic cancer by inhibiting autophagy and downregulating the rage/stat3 pathway | Authors: | Chen R.-J Lyu Y.-J Chen Y.-Y Lee Y.-C MIN-HSIUNG PAN Ho Y.-S Wang Y.-J. |
Keywords: | Apoptosis;Autophagy;Chloroquine;Pancreatic ductal adenocarcinoma;Pterostilbene;RAGE/STAT3;antineoplastic agent;chloroquine;mitogen activated protein kinase;MOK protein, human;pterostilbene;STAT3 protein;STAT3 protein, human;stilbene derivative;tumor antigen;autophagy;cell culture;cell proliferation;cell survival;chemistry;down regulation;drug effect;drug screening;human;metabolism;pancreas carcinoma;pancreas tumor;pathology;Antigens, Neoplasm;Antineoplastic Agents;Carcinoma, Pancreatic Ductal;Cell Proliferation;Cell Survival;Cells, Cultured;Down-Regulation;Drug Screening Assays, Antitumor;Humans;Mitogen-Activated Protein Kinases;Pancreatic Neoplasms;STAT3 Transcription Factor;Stilbenes | Issue Date: | 2021 | Journal Volume: | 26 | Journal Issue: | 21 | Source: | Molecules | Abstract: | The treatment of pancreatic ductal adenocarcinoma (PDAC) remains a huge challenge, because pro-survival signaling pathways—such as the receptor for advanced glycation end products (RAGE)/signal transducer and activator of transcription 3 (STAT3) pathway—are overexpressed in PDAC cells. Moreover, PDAC cells are highly resistant to chemotherapeutic agents because of autophagy induction. Therefore, autophagy and its modulated signaling pathways are attractive targets for developing novel therapeutic strategies for PDAC. Pterostilbene is a stilbenoid chemically related to resveratrol, and has potential for the treatment of cancers. Accordingly, we investigated whether the autophagy inhibitor chloroquine could potentiate the anticancer effect of pterostilbene in the PDAC cell lines MIA PaCa-2 and BxPC-3, as well as in an orthotopic animal model. The results indicated that pterostilbene combined with chloroquine significantly inhibited autophagy, decreased cell viability, and sensitized the cells to pterostilbene-induced apoptosis via downregulation of the RAGE/STAT3 and protein kinase B (AKT)/mammalian target of rapamycin (mTOR) pathways in PDAC cells. The results of the orthotopic animal model showed that pterostilbene combined with chloroquine significantly inhibited pancreatic cancer growth, delayed tumor quadrupling times, and inhibited autophagy and STAT3 in pancreatic tumors. In summary, the present study suggested the novel therapeutic strategy of pterostilbene combined with chloroquine against the growth of pancreatic ductal adenocarcinoma by inhibiting autophagy and downregulating the RAGE/STAT3 signaling pathways. ? 2021 by the authors. Licensee MDPI, Basel, Switzerland. |
URI: | https://www.scopus.com/inward/record.uri?eid=2-s2.0-85119601624&doi=10.3390%2fmolecules26216741&partnerID=40&md5=8803b08cd064b4510b2b532d86577950 https://scholars.lib.ntu.edu.tw/handle/123456789/606148 |
ISSN: | 14203049 | DOI: | 10.3390/molecules26216741 |
Appears in Collections: | 食品科技研究所 |
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