Phosphorylation of 4E-BP1 predicts sensitivity to everolimus in gastric cancer cells

We studied the effect of everolimus, an inhibitor of the mammalian target of rapamycin (mTOR) on human gastric cancer cell lines. Cell proliferation in 3 of 8 cell lines was effectively inhibited by everolimus. Basal phosphorylation level of 4E-BP1 (T37/46, T70) was significantly higher in everolimus-sensitive cells than in everolimus-resistant cells. In subcutaneous xenograft model, immunohistochemistry analysis revealed that everolimus-sensitive cells expressed high levels of phospho-4E-BP1 (T37/46). In conclusion, phosphorylation of 4E-BP1 may be a predictive biomarker of everolimus sensitivity in gastric cancer.

► Everolimus had anti-proliferative effect on gastric cancer cells without cell death. ► Everolimus sensitivity was not related to the capability to inhibit mTOR pathway. ► High phosphorylation level of 4E-BP1 was observed in everolimus-sensitive gastric cancer cell line. ► Everolimus-sensitive xenograft also showed high phosphorylation level of 4E-BP1. ► Basal phosphorylation status of 4E-BP1 could predict sensitivity to everolimus.