Anti-invasion, anti-proliferation and anoikis-sensitization activities of lapatinib in nasopharyngeal carcinoma cells
Publication in refereed journal

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其它資訊
摘要Nasopharyngeal cancer (NPC) is a highly prevalent and invasive head and neck cancer in Asia. Disease recurrence and distant metastasis account for major NPC deaths. Therefore, more effective therapy is needed. Lapatinib, a dual tyrosine kinase inhibitor (TKI) against both EGFR and HER-2, has been known to exert potent antitumor activity against several cancer models. Given that both EGFR and HER-2 are co-expressed in NPC, we hypothesized that dual targeting of EGFR and HER-2 by this small molecule EGFR/HER-2 TKI would elicit anti-tumor activity in NPC. Using in vitro models of NPC, we demonstrated that lapatinib was able to efficiently inhibit the phosphorylation of both EGFR and HER-2. This was accompanied by significant growth inhibition of NPC cells (with maximal growth inhibition > 90%). For the most lapatinib-sensitive cell line (HK1-LMP1, with IC(50) similar to 600 nM), which harbored the highest levels of both EGFR and HER-2, inhibition of cell growth was associated G(0)/G(1) cell cycle arrest, marked PARP cleavage, caspase-3 cleavage, as well as significant downregulation of several important survival proteins (e.g. survivin, Mcl-1 and cyclin D1). NPC cells are intrinsically invasive. We found that lapatinib was able to inhibit cellular invasion of both HK1-LMP1 and HONE-1 cells. Furthermore, our data demonstrated for the first time that lapatinib harbored potent anoikis-sensitization activity (i.e. sensitizing cancer cells to detachment-induced apoptosis) in human cancer cells overexpressing both EGFR and HER-2 (HK1-LMP1 and HK1). Taken together, our findings suggest that lapatinib is a promising anti-cancer agent for NPC with anti-invasion and anoikis-sensitization activities.
著者Lui VWY, Lau CPY, Ho K, Ng MHL, Cheng SH, Tsao SW, Tsang CM, Lei KIK, Chan ATC, Mok TSK
期刊名稱Investigational New Drugs
出版年份2011
月份12
卷號29
期次6
出版社SPRINGER
頁次1241 - 1252
國際標準期刊號0167-6997
電子國際標準期刊號1573-0646
語言英式英語
關鍵詞Lapatinib, Anti-invasion, Anoikis-sensitization, NPC
Web of Science 學科類別Oncology; ONCOLOGY; Pharmacology & Pharmacy; PHARMACOLOGY & PHARMACY

上次更新時間 2020-15-10 於 01:19