Dual effects for lovastatin in anaplastic thyroid cancer: the pivotal effect of transketolase (TKT) on lovastatin and tumor proliferation
Journal
Journal of Investigative Medicine
Journal Volume
66
Journal Issue
5
Pages
1
Date Issued
2018-06
Author(s)
Abstract
This study tested the hypothesis that the effects of lovastatin on anaplastic thyroid cancer cell growth are mediated by upregulation of transketolase (TKT) expression. The effects of lovastatin on TKT protein levels in ARO cells were determined using western blot and proteomic analyses. After treatment with lovastatin and oxythiamine, the in vitro and in vivo growth of ARO cells was determined using 3-(4,5-Dimethylthiazol-2-yl)-2,5- diphenyltetrazolium bromide (MTT) assays and tumor xenografts in nude mice. TKT protein expression in the ARO tumors was assessed using immunohistochemistry analysis. Proteomic analysis revealed that 25 μM lovastatin upregulated TKT expression. Co-treatment of ARO cells with 1 μM lovastatin + 1 μM oxythiamine increased TKT protein expression compared with
control levels; however, no differences were observed with 10 μM lovastatin + 1 μM oxythiamine. Furthermore, treatment with either oxythiamine or lovastatin alone reduced ARO tumor expression of TKT, as well as decreased ARO cell proliferation in vitro and tumor growth in vivo. However, mice treated with both lovastatin and oxythiamine at the
same time had tumor volumes similar to that of the untreated control group. We conclude that either lovastatin or oxythiamine reduced ARO cell growth; however, the combination of these drugs resulted in antagonism of ARO tumor growth.
Subjects
Anaplastic thyroid cancer, Lovastatin, Oxythiamine, Proliferation, Transketolase (TKT)
SDGs
Other Subjects
mevinolin; oxythiamine; transketolase; mevinolin; oxythiamine; transketolase; animal cell; apoptosis; ARO cell line; Article; cancer growth; cell proliferation; controlled study; drug effect; human; human cell; immunohistochemistry; in vitro study; in vivo study; matrix assisted laser desorption ionization time of flight mass spectrometry; mouse; MTT assay; nonhuman; protein analysis; protein expression; proteomics; thyroid follicular carcinoma; tumor growth; tumor volume; tumor xenograft; two dimensional gel electrophoresis; upregulation; Western blotting; animal; body weight; cell differentiation; enzymology; male; metabolism; nude mouse; pathology; thyroid carcinoma; tumor cell line; Animals; Apoptosis; Body Weight; Cell Differentiation; Cell Line, Tumor; Cell Proliferation; Lovastatin; Male; Mice, Nude; Oxythiamine; Proteomics; Thyroid Carcinoma, Anaplastic; Transketolase; Tumor Burden
Publisher
BMJ
Type
journal article
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