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. 2020 Jan-Feb;34(1):185-190.
doi: 10.21873/invivo.11760.

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

Jong Bin Kim  1 , Eun Yeol Yang  1 , Joohyun Woo  1 , Hyungju Kwon  2 , Woosung Lim  1 , Byung-In Moon  1
Affiliations

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

Jong Bin Kim et al. In Vivo. 2020 Jan-Feb.

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 p90RSK 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 p90RSK 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.

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Conflict of interest statement

The Authors declare that they have no conflicts of interest.

Figures

Figure 1
Figure 1. Morphologic changes of 8505C thyroid cancer cells after treatment with A) 10 nM, B) 100 nM, C) 1 μM, and D) 10 μM U0126 for 72 h.
Figure 2
Figure 2. Effect of U0126 treatment on cell proliferation of human thyroid cells. Cells with the RET-PTC1 rearrangement (TPC1), with a BRAF mutation (8505C), or normal human thyroid cells (HTori-3) were treated with 1 nM, 10 nM, 100 nM, 1 uM, and 10 uM of U0126 for 72 h. Cells treated with 0.01% ethanol were used as control cells. Results are presented as mean±S.E.M. The results are representative of four independent experiments performed in quadruplet. * and ***represent a significant effect of U0126 as compared to the control at p<0.05 and p<0.001, respectively.
Figure 3
Figure 3. Effect of sodium selenite treatment on cell viability in human thyroid cells. Cells were treated with distilled water (CTL) or with 1 μM, 5 μM, or 10 μM of sodium selenite for 72 h. Viable cells were counted in a Neubauer chamber. Results are presented as mean±SEM. The results are representative of four independent cultures performed in quadruplet. * and ***represent a significant effect of U0126 as compared to the control at p<0.05 and p<0.001, respectively.
Figure 4
Figure 4. Viability after sodium selenite and MEK-ERK inhibitor (U0126) treatment. Thyroid cells were treated with 0.01% ethanol (CTL), 1 μM, 5 μM sodium selenite, or 1 μM U0126 with 5 μM sodium selenite for 72 h. Viable cells were counted in a Neubauer chamber. Results are presented as mean±S.E.M. The results are representative of four independent cultures performed in quadruplet. ***represent a significant effect of U0126 with 5 μM sodium selenite as compared to 5 μM sodium selenite only at p<0.001.
Figure 5
Figure 5. Expression of ERK, p-ERK, and p90RSK after sodium selenite treatment for 72 h. A total of 5×105 of TPC1, 8505C, and HTori-3 cellss were seeded in DMEM containing 10% fetal bovine serum. Cell extracts were analyzed by western blot to detected the proteins indicated on the right.
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