Oncotarget

Research Papers:

Silencing IGFBP-2 decreases pancreatic cancer metastasis and enhances chemotherapeutic sensitivity

Huan Liu, Le Li, Hua Chen, Rui Kong, Shangha Pan, Jisheng Hu, Yongwei Wang, Yilong Li and Bei Sun _

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Oncotarget. 2017; 8:61674-61686. https://doi.org/10.18632/oncotarget.18669

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Abstract

Huan Liu1, Le Li1, Hua Chen1, Rui Kong1, Shangha Pan1, Jisheng Hu1, Yongwei Wang1, Yilong Li1 and Bei Sun1

1Department of Pancreatic and Biliary Surgery, The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, China

Correspondence to:

Bei Sun, email: sunbei70@tom.com

Keywords: IGFBP-2, pancreatic cancer, metastasis, Hedgehog, gemcitabine

Received: March 24, 2017     Accepted: May 11, 2017     Published: June 27, 2017

ABSTRACT

Pancreatic cancer has remained one of the most devastating and lethal malignancies characterized by local invasion, distant metastasis and a high degree of chemoresistance. Insulin-like growth factor binding protein 2 (IGFBP-2) is a member of the IGFBP family of proteins, and it is highly expressed in pancreatic cancer patients’ serum and tumor tissues. IGFBP-2 also mediates tumor cell growth, invasion and resistance, while the mechanisms remain unclear. In this study, we sought to determine the impact of IGFBP-2 expression on pancreatic cancer tumorigenesis and metastasis in vitro and in vivo. Wound healing, migration and invasion assays revealed that knockdown of IGFBP-2 inhibits cancer cell migration and invasion. Downregulation of IGFBP-2 attenuates EMT via increasing the E-cadherin and reducing the vimentin and N-cadherin. PTCH-1 is found contribute to the function of IGFBP-2 in suppressing metastasis and EMT of pancreatic cancer. Silencing IGFBP-2 inhibited invasion and metastatic properties, partially through inhibiting PTCH1 in pancreatic cancer. Additionally, inhibition of IGFBP-2 enhanced the sensitivity of pancreatic cancer cells to gemcitabine, suppressed tumor growth and potentiated the anti-tumor effect of gemcitabine in the orthotopic tumor model. Our results provide novel insight of IGFBP-2 as a promising target to inhibit the metastasis and overcome the chemoresistance in pancreatic cancer.


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