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Article

Lapatinib alters the malignant phenotype of osteosarcoma cells via downregulation of the activity of the HER2-PI3K/AKT-FASN axis in vitro

  • Authors:
    • Xin-Hua Long
    • Guo-Mei Zhang
    • Ai-Fen Peng
    • Qing-Feng Luo
    • Lin Zhang
    • Hui‑Cai Wen
    • Rong-Ping Zhou
    • Song Gao
    • Yang Zhou
    • Zhi-Li Liu
  • View Affiliations / Copyright

    Affiliations: Department of Orthopedics, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330006, P.R. China, Department of Orthopedics, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330006, P.R. China, Jiangxi University of Traditional Chinese Medicine, Nanchang, Jiangxi 330006, P.R. China , Department of Pathology, Cancer Hospital of Jiangxi Province, Nanchang, Jiangxi 330006, P.R. China
  • Pages: 328-334
    |
    Published online on: October 29, 2013
       https://doi.org/10.3892/or.2013.2825
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Abstract

Lapatinib, an inhibitor of human epidermal growth factor receptor 2 (HER2) phosphorylation, has been reported to inhibit several types of tumors such as HER2-overexpressing breast cancer. However, the effect of lapatinib on the malignant phenotype of human osteosarcoma (OS) cells and the potential molecular mechanisms remain unclear. To elucidate the effect of lapatinib on OS, two OS cell lines, U2-OS and MG-63, were utilized in the present study. Various concentrations of lapatinib were used to treat OS cells for different time durations. Cell proliferation was evaluated by MTT and colony formation assays. Flow cytometry (FCM) was used to evaluate cell apoptosis. Wound healing and Transwell invasion assays were performed to examine the migratory and invasive abilities of the cells. To investigate the possible molecular mechanisms involved, the expression of p-HER2, phosphatidylinositol 3-kinase (PI3K), p-AKT, AKT and fatty acid synthase (FASN) protein was detected by western blotting. MTT assays showed that lapatinib inhibited the proliferation of U2-OS and MG-63 cells in a dose- and time-dependent manner, and the rate of colony formation of the lapatinib-treated cells was significantly lower when compared to those cells not treated with lapatinib in both cell lines. FCM assay revealed a significantly higher apoptotic rate in the lapatinib-treated OS cells. Wound healing and Transwell invasion assays revealed that the migratory and invasive abilities of OS cells were significantly inhibited by lapatinib (P<0.05). Western blotting showed that lapatinib suppressed the activity of HER2-PI3K/AKT-FASN in U2-OS and MG-63 cells in vitro. These results suggest that lapatinib may alter the malignant phenotype of OS cells via downregulation of the activity of the HER2-PI3K/AKT-FASN signaling pathway in vitro. Thus, lapatinib may be an effective chemotherapeutic agent for the treatment of osteosarcoma.
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Copy and paste a formatted citation
Spandidos Publications style
Long X, Zhang G, Peng A, Luo Q, Zhang L, Wen HC, Zhou R, Gao S, Zhou Y, Liu Z, Liu Z, et al: Lapatinib alters the malignant phenotype of osteosarcoma cells via downregulation of the activity of the HER2-PI3K/AKT-FASN axis in vitro. Oncol Rep 31: 328-334, 2014.
APA
Long, X., Zhang, G., Peng, A., Luo, Q., Zhang, L., Wen, H. ... Liu, Z. (2014). Lapatinib alters the malignant phenotype of osteosarcoma cells via downregulation of the activity of the HER2-PI3K/AKT-FASN axis in vitro. Oncology Reports, 31, 328-334. https://doi.org/10.3892/or.2013.2825
MLA
Long, X., Zhang, G., Peng, A., Luo, Q., Zhang, L., Wen, H., Zhou, R., Gao, S., Zhou, Y., Liu, Z."Lapatinib alters the malignant phenotype of osteosarcoma cells via downregulation of the activity of the HER2-PI3K/AKT-FASN axis in vitro". Oncology Reports 31.1 (2014): 328-334.
Chicago
Long, X., Zhang, G., Peng, A., Luo, Q., Zhang, L., Wen, H., Zhou, R., Gao, S., Zhou, Y., Liu, Z."Lapatinib alters the malignant phenotype of osteosarcoma cells via downregulation of the activity of the HER2-PI3K/AKT-FASN axis in vitro". Oncology Reports 31, no. 1 (2014): 328-334. https://doi.org/10.3892/or.2013.2825
Copy and paste a formatted citation
x
Spandidos Publications style
Long X, Zhang G, Peng A, Luo Q, Zhang L, Wen HC, Zhou R, Gao S, Zhou Y, Liu Z, Liu Z, et al: Lapatinib alters the malignant phenotype of osteosarcoma cells via downregulation of the activity of the HER2-PI3K/AKT-FASN axis in vitro. Oncol Rep 31: 328-334, 2014.
APA
Long, X., Zhang, G., Peng, A., Luo, Q., Zhang, L., Wen, H. ... Liu, Z. (2014). Lapatinib alters the malignant phenotype of osteosarcoma cells via downregulation of the activity of the HER2-PI3K/AKT-FASN axis in vitro. Oncology Reports, 31, 328-334. https://doi.org/10.3892/or.2013.2825
MLA
Long, X., Zhang, G., Peng, A., Luo, Q., Zhang, L., Wen, H., Zhou, R., Gao, S., Zhou, Y., Liu, Z."Lapatinib alters the malignant phenotype of osteosarcoma cells via downregulation of the activity of the HER2-PI3K/AKT-FASN axis in vitro". Oncology Reports 31.1 (2014): 328-334.
Chicago
Long, X., Zhang, G., Peng, A., Luo, Q., Zhang, L., Wen, H., Zhou, R., Gao, S., Zhou, Y., Liu, Z."Lapatinib alters the malignant phenotype of osteosarcoma cells via downregulation of the activity of the HER2-PI3K/AKT-FASN axis in vitro". Oncology Reports 31, no. 1 (2014): 328-334. https://doi.org/10.3892/or.2013.2825
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