Downregulation of ASPP2 in pancreatic cancer cells contributes to increased resistance to gemcitabine through autophagy activationReport as inadecuate




Downregulation of ASPP2 in pancreatic cancer cells contributes to increased resistance to gemcitabine through autophagy activation - Download this document for free, or read online. Document in PDF available to download.

Molecular Cancer

, 14:177

First Online: 05 October 2015Received: 08 April 2015Accepted: 21 September 2015DOI: 10.1186-s12943-015-0447-5

Cite this article as: Song, B., Bian, Q., Zhang, YJ. et al. Mol Cancer 2015 14: 177. doi:10.1186-s12943-015-0447-5

Abstract

BackgroundApoptosis-stimulating of p53 protein 2 ASPP2 is one of the ASPP family members and it has been reported to be associated with human cancer. However, the role of it in pancreatic cancer is still not clear.

MethodsWe analyzed the expression level of ASPP2 in cancer tissue samples with RT-qPCR, Western Blotting assay and immunohistochemistry staining. We studied the biological function of ASPP2 and its mechanism with gene overexpression and gene silencing technologies. We determined the sensitivity of pancreatic cells with differential ASPP2 level to gemcitabine and whether autophagy inhibition affected the gemcitabine resistance, both in vitro and in vivo.

ResultsExpression of ASPP2 was downregulated in cancerous tissues in comparison with para-cancerous tissues. ASPP2 expression was linked to clinical outcomes in patients and down-regulation of ASPP2 increased cell proliferation, autophagic flux, the activity of AMP Kinase of pancreatic cancer cells and vice versa. Knockdown of ASPP2 results in increased resistance to gemcitabine, which was attributed to the enhanced autophagy.

ConclusionsASSP2 expression is lower in cancerous tissues and decreased ASPP2 lead to higher cancer cells proliferation and autophagic flux, which contribute to the gemcitabine resistance.

KeywordsPancreatic cancer ASSP2 Proliferation Autophagy Drug resistance Gemcitabine AbbreviationsASPP2Apoptosis-stimulating of p53 protein 2

RT-qPCRReverse Transcription Quantitative Polymerase Chain Reaction

shRNAShort hairpin RNA

AMPKAdenosine 5’-monophosphate AMP-activated protein kinase

PCPancreatic cancer

ATGAutophagy-related

GFPGreen Fluorescent Protein

RFPRed fluorescent protein

CQChloroquine

Bin Song, Qi Bian and Yi-Jie Zhang contributed equally to this work.

Electronic supplementary materialThe online version of this article doi:10.1186-s12943-015-0447-5 contains supplementary material, which is available to authorized users.

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Author: Bin Song - Qi Bian - Yi-Jie Zhang - Cheng-Hao Shao - Gang Li - An-An Liu - Wei Jing - Rui Liu - Ying-Qi Zhou - Gang Jin

Source: https://link.springer.com/







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