Open Access

Effects of lapatinib on cell proliferation and apoptosis in NB4 cells

  • Authors:
    • Lu Liu
    • Liang Zhong
    • Yi Zhao
    • Min Chen
    • Shifei Yao
    • Lianwen Li
    • Chunlan Xiao
    • Zhiling Shan
    • Liugen Gan
    • Ting Xu
    • Beizhong Liu
  • View Affiliations

  • Published online on: November 3, 2017     https://doi.org/10.3892/ol.2017.7342
  • Pages: 235-242
  • Copyright: © Liu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Acute promyelocytic leukemia (APL), characterized by the presence of the promyelocytic leukemia (PML)‑retinoic acid α receptor (RARα) fusion protein, responds to treatment with all‑trans retinoic acid (ATRA) and arsenic trioxide (ATO). However, drug resistance and side effects restrict the application of these reagents. Hence, the development of novel therapeutic drugs for APL treatment is critical. Lapatinib, a small‑molecule tyrosine kinase inhibitor, has been used in the treatment of different tumors. However, it is unclear whether lapatinib exerts antitumor effects on APL. The present study investigated the antitumor effects and potential mechanisms of lapatinib on NB4 cells derived from APL. Cell Counting Kit‑8 assay and colony forming analysis indicated that lapatinib inhibited NB4 cell proliferation in a dose‑dependent manner. Flow cytometry analysis revealed that lapatinib induced cell cycle arrest at the S phase and promoted cell apoptosis. Furthermore, Liu's staining and Hoechst 33258 staining revelaed that lapatinib treatment induced an apoptotic nuclear phenomenon. Furthermore, lapatinib induced apoptosis by decreasing Bcl‑2 and PML‑RARα levels, and by increasing the levels of Bax, cleaved PARP, cleaved caspase‑3 and cleaved caspase‑9. In addition, lapatinib increased the levels of phospho‑p38 MAPK and phospho‑JNK, and decreased the levels of phospho‑Akt. The p38 inhibitor PD169316 partially blocked lapatinib‑induced proliferation inhibition and apoptosis, whereas the JNK inhibitor SP600125 had no such effects. Therefore, treatment with lapatinib may be a promising strategy for APL therapy.
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January-2018
Volume 15 Issue 1

Print ISSN: 1792-1074
Online ISSN:1792-1082

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Spandidos Publications style
Liu L, Zhong L, Zhao Y, Chen M, Yao S, Li L, Xiao C, Shan Z, Gan L, Xu T, Xu T, et al: Effects of lapatinib on cell proliferation and apoptosis in NB4 cells. Oncol Lett 15: 235-242, 2018
APA
Liu, L., Zhong, L., Zhao, Y., Chen, M., Yao, S., Li, L. ... Liu, B. (2018). Effects of lapatinib on cell proliferation and apoptosis in NB4 cells. Oncology Letters, 15, 235-242. https://doi.org/10.3892/ol.2017.7342
MLA
Liu, L., Zhong, L., Zhao, Y., Chen, M., Yao, S., Li, L., Xiao, C., Shan, Z., Gan, L., Xu, T., Liu, B."Effects of lapatinib on cell proliferation and apoptosis in NB4 cells". Oncology Letters 15.1 (2018): 235-242.
Chicago
Liu, L., Zhong, L., Zhao, Y., Chen, M., Yao, S., Li, L., Xiao, C., Shan, Z., Gan, L., Xu, T., Liu, B."Effects of lapatinib on cell proliferation and apoptosis in NB4 cells". Oncology Letters 15, no. 1 (2018): 235-242. https://doi.org/10.3892/ol.2017.7342