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沉默IGFBP - 2可降低胰腺癌转移并增强化疗敏感性。

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

作者信息

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

机构信息

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

出版信息

Oncotarget. 2017 Jun 27;8(37):61674-61686. doi: 10.18632/oncotarget.18669. eCollection 2017 Sep 22.

DOI:10.18632/oncotarget.18669
PMID:28977895
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5617455/
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 and . 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.

摘要

胰腺癌一直是最具破坏性和致命性的恶性肿瘤之一，其特征为局部侵袭、远处转移和高度化疗耐药性。胰岛素样生长因子结合蛋白2（IGFBP-2）是IGFBP蛋白家族的成员，在胰腺癌患者的血清和肿瘤组织中高表达。IGFBP-2还介导肿瘤细胞的生长、侵袭和耐药性，但其机制尚不清楚。在本研究中，我们试图确定IGFBP-2表达对胰腺癌发生和转移的影响。伤口愈合、迁移和侵袭试验表明，敲低IGFBP-2可抑制癌细胞的迁移和侵袭。IGFBP-2的下调通过增加E-钙黏蛋白并减少波形蛋白和N-钙黏蛋白来减弱上皮-间质转化（EMT）。发现PTCH-1有助于IGFBP-2在抑制胰腺癌转移和EMT中的作用。沉默IGFBP-2可抑制侵袭和转移特性，部分是通过抑制胰腺癌中的PTCH1实现的。此外，抑制IGFBP-2可增强胰腺癌细胞对吉西他滨的敏感性，抑制肿瘤生长，并增强吉西他滨在原位肿瘤模型中的抗肿瘤作用。我们的结果为IGFBP-2作为抑制胰腺癌转移和克服化疗耐药性的有前景靶点提供了新的见解。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f61e/5617455/fbd53c7b6dda/oncotarget-08-61674-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f61e/5617455/9f768ba8a135/oncotarget-08-61674-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f61e/5617455/1fe92eba5cdb/oncotarget-08-61674-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f61e/5617455/a17d890c2bd9/oncotarget-08-61674-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f61e/5617455/4312719adef0/oncotarget-08-61674-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f61e/5617455/579df466f21a/oncotarget-08-61674-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f61e/5617455/fbd53c7b6dda/oncotarget-08-61674-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f61e/5617455/9f768ba8a135/oncotarget-08-61674-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f61e/5617455/1fe92eba5cdb/oncotarget-08-61674-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f61e/5617455/a17d890c2bd9/oncotarget-08-61674-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f61e/5617455/4312719adef0/oncotarget-08-61674-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f61e/5617455/579df466f21a/oncotarget-08-61674-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f61e/5617455/fbd53c7b6dda/oncotarget-08-61674-g006.jpg

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