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Anaplastic lymphoma kinase inhibitor NVP‑TAE684 suppresses the proliferation of human pancreatic adenocarcinoma cells

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Main Author: Duong, Hong-Quan
Other Authors: Than, Van Thai
Format: Article
Language:English
Published: Oncology Reports 2021
Online Access:https://www.spandidos-publications.com/10.3892/or.2021.7979
https://dlib.phenikaa-uni.edu.vn/handle/PNK/1769
https://doi.org/10.3892/or.2021.7979
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spelling oai:localhost:PNK-17692022-08-17T05:54:42Z Anaplastic lymphoma kinase inhibitor NVP‑TAE684 suppresses the proliferation of human pancreatic adenocarcinoma cells Duong, Hong-Quan Than, Van Thai Nguyen, Huyen-Trang Nguyen, Phuong-Thoa Ha Thi, Huyen Trang Bui, Thi Ngoc Ha Dang, Vu Phuong Linh Dinh, Thi-Thanh You, Kyu Sic Dang, The-Hung Seong, Yeon-Sun Q2 Anaplastic lymphoma kinase (ALK) is known to be an important therapeutic target in various types of cancer. NVP‑TAE684, a well‑known inhibitor of ALK, was revealed to exert antitumor effects in several different malignancies. However, the molecular mechanisms responsible for these antitumor effects in cancer cells, including pancreatic adenocarcinoma cells, remain unknown. In the present study, NVP‑TAE684 was investigated for its antitumor effects towards pancreatic adenocarcinoma cells. MTT assay, western blot analysis, flow cytometry, caspase‑3/7 activity assay and Trypan blue exclusion assay were used and it was revealed that NVP‑TAE684 suppressed the proliferation of seven human pancreatic adenocarcinoma cell lines (AsPC‑1, Panc‑1, MIA PaCa‑2, Capan‑1, CFPAC‑1, Colo‑357 and BxPC‑3), and significantly increased G2/M arrest and apoptotic cell death. Furthermore, NVP‑TAE684 inhibited the phosphorylation of ALK at Y1604, as well as that of downstream mediators such as AKT (S473) and ERK1/2 (Y202/T204). Notably, knocking down ALK with siRNAs also decreased proliferation and promoted G2/M arrest and apoptosis. Furthermore, inhibition of ALK with NVP‑TAE684 or siRNA synergistically enhanced gemcitabine‑induced cell death by inducing apoptosis. In conclusion, the findings of the present study indicated that NVP‑TAE684 exerted its antitumor effects by inducing G2/M arrest and apoptosis via the inhibition of the ALK signaling pathway, and suggests its potential use as an antitumor agent against pancreatic adenocarcinoma. 2021-06-15T04:15:47Z 2021-06-15T04:15:47Z 2021 Article Working Paper https://www.spandidos-publications.com/10.3892/or.2021.7979 https://dlib.phenikaa-uni.edu.vn/handle/PNK/1769 https://doi.org/10.3892/or.2021.7979 en Oncology Reports
institution Digital Phenikaa
collection Digital Phenikaa
language English
description Q2
author2 Than, Van Thai
author_facet Than, Van Thai
Duong, Hong-Quan
format Article
author Duong, Hong-Quan
spellingShingle Duong, Hong-Quan
Anaplastic lymphoma kinase inhibitor NVP‑TAE684 suppresses the proliferation of human pancreatic adenocarcinoma cells
author_sort Duong, Hong-Quan
title Anaplastic lymphoma kinase inhibitor NVP‑TAE684 suppresses the proliferation of human pancreatic adenocarcinoma cells
title_short Anaplastic lymphoma kinase inhibitor NVP‑TAE684 suppresses the proliferation of human pancreatic adenocarcinoma cells
title_full Anaplastic lymphoma kinase inhibitor NVP‑TAE684 suppresses the proliferation of human pancreatic adenocarcinoma cells
title_fullStr Anaplastic lymphoma kinase inhibitor NVP‑TAE684 suppresses the proliferation of human pancreatic adenocarcinoma cells
title_full_unstemmed Anaplastic lymphoma kinase inhibitor NVP‑TAE684 suppresses the proliferation of human pancreatic adenocarcinoma cells
title_sort anaplastic lymphoma kinase inhibitor nvp‑tae684 suppresses the proliferation of human pancreatic adenocarcinoma cells
publisher Oncology Reports
publishDate 2021
url https://www.spandidos-publications.com/10.3892/or.2021.7979
https://dlib.phenikaa-uni.edu.vn/handle/PNK/1769
https://doi.org/10.3892/or.2021.7979
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score 8.8926115

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