A synergistic anti-cancer effect of troglitazone and lovastatin in a human anaplastic thyroid cancer cell line and in a mouse xenograft model

Wen Bin Zhong, Yuan Chin Tsai, Li Han Chin, Jen Ho Tseng, Li Wen Tang, Steve Horng, Yu Ching Fan, Sung Po Hsu

研究成果: 雜誌貢獻文章同行評審

10 引文 斯高帕斯(Scopus)

摘要

Anaplastic thyroid cancer (ATC) is a malignant subtype of thyroid cancers and its mechanism of development remains inconclusive. Importantly, there is no effective strategy for treatment since ATC is not responsive to conventional therapies, including radioactive iodine therapy and thyroid-stimulating hormone suppression. Here, we report that a combinational approach consisting of drugs designed for targeting lipid metabolism, lovastatin (an inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A reductase, HMGCR) and troglitazone (an agonist of peroxisome proliferator-activated receptor gamma, PPARγ), exhibits anti-proliferation in cell culture systems and leads to tumor regression in a mouse xenograft model. The composition contains a sub-lethal concentration of both drugs and exhibits low toxicity to certain types of normal cells. Our results support a hypothesis that the inhibitory effect of the combination is partly through a cell cycle arrest at G0/G1 phase, as evidenced by the induction of cyclin-dependent kinase inhibitors, p21cip and p27kip, and the reduction of hyperphosphorylated retinoblastoma protein (pp-Rb)-E2F1 signaling. Therefore, targeting two pathways involved in lipid metabolism may provide a new direction for treating ATC.
原文英語
文章編號1834
期刊International Journal of Molecular Sciences
19
發行號7
DOIs
出版狀態已發佈 - 七月 1 2018

ASJC Scopus subject areas

  • 催化
  • 分子生物學
  • 光譜
  • 電腦科學應用
  • 物理與理論化學
  • 有機化學
  • 無機化學

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