Dexamethasone affects cell growth/apoptosis/chemosensitivity of colon cancer via glucocorticoid receptor α/NF-κB.

Glucocorticoids are effective to treat lymphoma and leukemia. Their effect in colon cancer remains far from clear. Here, we found that glucocorticoid receptor (GR) α protein level was dramatically lower in colon cancer than in lymphoma. Colon cell lines LoVo and HCT116 were GRα-rich and GRα was not detectable in HT29 or SW480. Dexamethasone significantly inhibited cell growth of GRα-rich cell lines and did not significantly affect GRα-negative cell lines. Dexamethasone induced apoptosis and increased chemosensitivity of GRα-rich cell lines. Knockdown of GRα significantly attenuated dexamethasone effects on cell growth, apoptosis and chemosensitivity. NF-κB p65 significantly correlated with GRα in colon cancer samples. Dexamethasone decreased NF-κB p65 activity. Knockdown of NF-κB p65 increased apoptosis. Our data demonstrate GRα protein level is dramatically lower in colon cancer than in lymphoma. Dexamethasone inhibits cell growth, induces apoptosis and enhances chemosensitivity in colon cancer, at least partly, via GRα and NF-κB.