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Article

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

  • Authors:
    • Hong-Quan Duong
    • Van Thai Than
    • Huyen-Trang Nguyen
    • Phuong-Thoa Nguyen
    • Huyen Trang Ha Thi
    • Thi Ngoc Ha Bui
    • Vu Phuong Linh Dang
    • Thi-Thanh Dinh
    • Kyu Sic You
    • The-Hung Dang
    • Yeon-Sun Seong
  • View Affiliations / Copyright

    Affiliations: Laboratory Center, Hanoi University of Public Health, Hanoi 100000, Vietnam, Faculty of Biotechnology, Chemistry and Environmental Engineering, Phenikaa University, Hanoi 100000, Vietnam, Department of Biochemistry, College of Medicine, Dankook University, Cheonan‑si, Chungcheongnam‑do 31116, Republic of Korea
  • Article Number: 28
    |
    Published online on: February 18, 2021
       https://doi.org/10.3892/or.2021.7979
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Abstract

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.
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Copy and paste a formatted citation
Spandidos Publications style
Duong H, Than VT, Nguyen H, Nguyen P, Thi HT, Bui TN, Dang VP, Dinh T, You KS, Dang T, Dang T, et al: Anaplastic lymphoma kinase inhibitor NVP‑TAE684 suppresses the proliferation of human pancreatic adenocarcinoma cells. Oncol Rep 45: 28, 2021.
APA
Duong, H., Than, V.T., Nguyen, H., Nguyen, P., Thi, H.T., Bui, T.N. ... Seong, Y. (2021). Anaplastic lymphoma kinase inhibitor NVP‑TAE684 suppresses the proliferation of human pancreatic adenocarcinoma cells. Oncology Reports, 45, 28. https://doi.org/10.3892/or.2021.7979
MLA
Duong, H., Than, V. T., Nguyen, H., Nguyen, P., Thi, H. T., Bui, T. N., Dang, V. P., Dinh, T., You, K. S., Dang, T., Seong, Y."Anaplastic lymphoma kinase inhibitor NVP‑TAE684 suppresses the proliferation of human pancreatic adenocarcinoma cells". Oncology Reports 45.4 (2021): 28.
Chicago
Duong, H., Than, V. T., Nguyen, H., Nguyen, P., Thi, H. T., Bui, T. N., Dang, V. P., Dinh, T., You, K. S., Dang, T., Seong, Y."Anaplastic lymphoma kinase inhibitor NVP‑TAE684 suppresses the proliferation of human pancreatic adenocarcinoma cells". Oncology Reports 45, no. 4 (2021): 28. https://doi.org/10.3892/or.2021.7979
Copy and paste a formatted citation
x
Spandidos Publications style
Duong H, Than VT, Nguyen H, Nguyen P, Thi HT, Bui TN, Dang VP, Dinh T, You KS, Dang T, Dang T, et al: Anaplastic lymphoma kinase inhibitor NVP‑TAE684 suppresses the proliferation of human pancreatic adenocarcinoma cells. Oncol Rep 45: 28, 2021.
APA
Duong, H., Than, V.T., Nguyen, H., Nguyen, P., Thi, H.T., Bui, T.N. ... Seong, Y. (2021). Anaplastic lymphoma kinase inhibitor NVP‑TAE684 suppresses the proliferation of human pancreatic adenocarcinoma cells. Oncology Reports, 45, 28. https://doi.org/10.3892/or.2021.7979
MLA
Duong, H., Than, V. T., Nguyen, H., Nguyen, P., Thi, H. T., Bui, T. N., Dang, V. P., Dinh, T., You, K. S., Dang, T., Seong, Y."Anaplastic lymphoma kinase inhibitor NVP‑TAE684 suppresses the proliferation of human pancreatic adenocarcinoma cells". Oncology Reports 45.4 (2021): 28.
Chicago
Duong, H., Than, V. T., Nguyen, H., Nguyen, P., Thi, H. T., Bui, T. N., Dang, V. P., Dinh, T., You, K. S., Dang, T., Seong, Y."Anaplastic lymphoma kinase inhibitor NVP‑TAE684 suppresses the proliferation of human pancreatic adenocarcinoma cells". Oncology Reports 45, no. 4 (2021): 28. https://doi.org/10.3892/or.2021.7979
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