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Dual effects for lovastatin in anaplastic thyroid cancer: the pivotal effect of transketolase (TKT) on lovastatin and tumor proliferation
  1. Chih-Yuan Wang1,
  2. Hao-Ai Shui2,
  3. Tien-Chun Chang1
  1. 1 Department of Internal Medicine, National Taiwan University Hospital and College of Medicine, National Taiwan University, Taipei, Taiwan
  2. 2 Graduate Institute of Medical Sciences, National Defense Medical Center, Taipei, Taiwan
  1. Correspondence to Dr Chih-Yuan Wang, Department of Internal Medicine, National Taiwan University Hospital and College of Medicine, National Taiwan University, Taipei 10617, Taiwan; cyw1965{at}gmail.com

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.

  • anaplastic thyroid cancer
  • lovastatin
  • oxythiamine
  • proliferation
  • transketolase (TKT)

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Footnotes

  • Contributors C-YW: study concepts, study design, data analysis and manuscript preparation. H-AS: study concepts, study design, data analysis, data acquisition and data analysis. T-CC: study concepts and manuscript review.

  • Competing interests None declared.

  • Provenance and peer review Not commissioned; externally peer reviewed.

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