Chloroquine potentiates the anticancer effect of pterostilbene on pancreatic cancer by inhibiting autophagy and downregulating the rage/stat3 pathway

Rong Jane Chen, Yi Jhen Lyu, Yu Ying Chen, Yen Chien Lee, Min Hsiung Pan, Yuan Soon Ho, Ying Jan Wang

研究成果: 雜誌貢獻文章同行評審

1 引文 斯高帕斯(Scopus)

摘要

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.

原文英語
文章編號6741
期刊Molecules
26
發行號21
DOIs
出版狀態已發佈 - 11月 1 2021

ASJC Scopus subject areas

  • 分析化學
  • 化學(雜項)
  • 分子醫學
  • 藥學科學
  • 藥物發現
  • 物理與理論化學
  • 有機化學

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