Sodium Selenite Enhanced the Anti-proliferative Effect of MEK-ERK Inhibitor in Thyroid Cancer Cells

Abstract

Background/aim: MEK-ERK pathway plays major roles in the progression of thyroid cancer, while the use of MEK-ERK inhibitors has been limited by its toxicity. We investigated the effect of sodium selenite as an adjunct for MEK-ERK inhibitors to avoid the toxicity of ERK inhibitors.

Materials and methods: TPC1, 8505C and HTori-3 cells were treated with U0126 (MEK-ERK inhibitor) and cell viability was counted in the Neubauer chamber. The synergistic effects of sodium selenite and U0126 were also measured. The expression of ERK, p-ERK, and p90^RSK was determined by western blot.

Results: Treatment with U0126 inhibited proliferation of TPC1 and 8505C cells in a dose-dependent manner. When 5 μM sodium selenite was added to 1 μM U0126, relative cell survival further decreased. Decreased expression of p90^RSK indicated that sodium selenite down-regulated ERK signaling in thyroid cancer cells.

Conclusion: The combination of U0126 and sodium selenite inhibited proliferation of thyroid cancer cells through ERK inhibition.

Keywords: ERK pathway; MEK-ERK inhibitor; Selenium; U0126; thyroid cancer.