کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2599108 1133183 2014 9 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Par-4 downregulation confers cisplatin resistance in pancreatic cancer cells via PI3K/Akt pathway-dependent EMT
موضوعات مرتبط
علوم زیستی و بیوفناوری علوم محیط زیست بهداشت، سم شناسی و جهش زایی
پیش نمایش صفحه اول مقاله
Par-4 downregulation confers cisplatin resistance in pancreatic cancer cells via PI3K/Akt pathway-dependent EMT
چکیده انگلیسی


• CDDP resistance correlates with EMT in pancreatic cancer cells.
• Par-4 is downregulated during development of CDDP resistance.
• Par-4 downregulation confers CDDP resistance via Akt-mediated EMT.

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.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Toxicology Letters - Volume 224, Issue 1, 3 January 2014, Pages 7–15
نویسندگان
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