Second-generation Src/Abl inhibitor bosutinib effectively induces apoptosis in human esophageal squamous cell carcinoma (ESCC) cells via inhibiting Src/Abl signaling

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.

UPP1 promotes lung adenocarcinoma progression through the induction of an immunosuppressive microenvironment

“…Based on the bioinformatics-based screening and validations using both in vitro and in vivo models, we revealed a notable association between high UPP1 expression and increased sensitivity to Bosutinib and Dasatinib. Bosutinib is a selective inhibitor designed to target the Src family kinases and has been approved for the treatment of chronic myeloid leukemia (CML) in adults 74,75 . Dasatinib, on the other hand, has a broader range, inhibiting not just the Src family kinases but also several other kinases 76,77 .…”

Development and Validation of a Ferroptosis-Related Gene Signature and Nomogram for Predicting the Prognosis of Esophageal Squamous Cell Carcinoma

“…Dasatinib enhances cisplatin sensitivity in ESCC cells via suppression of the PI3K/AKT and Stat3 pathways ( Chen et al, 2015 ). Bosutinib effectively induces apoptosis in ESCC cells by inhibiting Src/Abl signaling ( Ha et al, 2020 ). In our present study, we demonstrated SRC was overexpressed in ESCC tissues compared with normal esophageal mucosa.…”