Neoplasma Vol.67, No.1, p.54–60, 2020
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Title: Second-generation Src/Abl inhibitor bosutinib effectively induces apoptosis in human esophageal squamous cell carcinoma (ESCC) cells via inhibiting Src/Abl signaling |
Author: Y. N. E. Ha, Y. Dai, D. Wufuer, M. Pidayi, G. Anasihan, L. Chen |
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Abstract: Esophageal cancer is a prevalent type of cancer worldwide and is ranked sixth among cancer-associated mortalities. Aberrant activation of the non-receptor tyrosine kinase Src and c-Abl contribute to the progression of ESCC. Thus, targeting these kinases to treat ESCC is a promising strategy. In this paper, we report that the potent dual Src/Abl inhibitor bosutinib exerts anti-tumor effects on ESCC. Bosutinib inhibits ESCC cell proliferation in a dose-dependent manner. Furthermore, bosutinib suppresses the colony formation ability of ESCC cells. Mechanistically, bosutinib effectively inhibits c-Abl and Src and its downstream signaling pathways, PI3K/AKT/mTOR and JAK/STAT3. In addition, bosutinib enhances the cytotoxic effects of doxorubicin on ESCC cells. In summary, our results reveal that Src and Abl are potential therapeutic targets in ESCC and that the novel Src/Abl inhibitor bosutinib alone or in combination with other chemotherapeutic agents may be a viable option for treating ESCC patients.
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Keywords: esophageal cancer, Src/Abl inhibitor, bosutinib, doxorubicin, chemotherapeutic agents |
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Published online: 29-Jan-2020
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Year: 2020, Volume: 67, Issue: 1 |
Page From: 54, Page To: 60 |
doi:10.4149/neo_2019_190131N94
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