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• W2074191719 endingPage "15" @default.
• W2074191719 startingPage "7" @default.
• W2074191719 abstract "Cisplatin (CDDP) efficiency in pancreatic cancer therapy is limited due to development of drug resistance. However, the comprehensive mechanisms remain largely unclear. In this study, we first established a CDDP-resistant pancreatic cancer cell line-BXPC-3/CDDP from its parental cell line-BXPC-3. The results showed that CDDP resistance in BXPC-3/CDDP cells correlates with changes in cellular EMT phenotypes. Prostate apoptosis response-4 (Par-4) expression at both mRNA and protein levels were reduced in CDDP-resistant BXPC-3/CDDP cells compared with that in BXPC-3 cells. Ectopic expression of Par-4 reversed EMT and CDDP resistance in BXPC-3/CDDP cells. In BXPC-3 cells, knockdown of Par-4 expression induces EMT and CDDP insensitivity, however, these effects were blocked by inhibition of PI3K/Akt pathway using LY294002. Furthermore, Par-4 knockdown could significantly stimulate PI3K/Akt signaling in BXPC-3 cells. In vivo studies, xenograft BXPC-3 tumors were sensitive to CDDP treatment. Treatment with CDDP alone had little effect on the growth of Par-4 siRNA-transfected BXPC-3 tumors in nude mice and the survival rate compared with control. Inhibition of PI3K/Akt pathway using LY294002 reversed CDDP resistance in Par-4 siRNA-transfected BXPC-3 tumors. In conclusion, these results indicate that Par-4 downregulation confers CDDP resistance via PI3K/Akt pathway-dependent EMT in BXPC-3 cells. Therefore, Par-4 may be a potential target for overcoming CDDP resistance in pancreatic cancer." @default.
• W2074191719 created "2016-06-24" @default.
• W2074191719 creator A5006919028 @default.
• W2074191719 creator A5008467332 @default.
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• W2074191719 date "2014-01-01" @default.
• W2074191719 modified "2023-10-14" @default.
• W2074191719 title "Par-4 downregulation confers cisplatin resistance in pancreatic cancer cells via PI3K/Akt pathway-dependent EMT" @default.
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• W2074191719 doi "https://doi.org/10.1016/j.toxlet.2013.10.008" @default.
• W2074191719 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/24144893" @default.
• W2074191719 hasPublicationYear "2014" @default.
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