The role of atorvastatin in suppressing tumor growth of uterine fibroids

Zhaojun Shen, Saisai Li, Bo Sheng, Qi Shen, Luzhe Sun, Haiyan Zhu, Xueqiong Zhu

Research output: Contribution to journalArticle

2 Scopus citations

Abstract

Background: Medical therapeutic options remain quite limited for uterine fibroids treatment. Statins, competitive inhibitors of 3-hydroxy-3-methylglutaryl-coenzyme A reductase, have anti-tumoral effects on multiple cancer types, however, little is known about their effects on uterine fibroids. Methods: Initially, we conducted a retrospective study of 120 patients with uterine fibroids and hyperlipidemia from the Second Affiliated Hospital of Wenzhou Medical University. Then, we evaluated the effect of atorvastatin on proliferation and apoptosis both in immortalized uterine fibroids cells and primary uterine fibroids cells. Furthermore, the molecular mechanism by which atorvastatin suppressed uterine fibroids cell growth was explored. Results: Our results showed that atorvastatin use for 1 or 2 years significantly suppressed growth of uterine fibroids. Atorvastatin inhibited the proliferation of immortalized and primary uterine fibroids cells in a dose and time-dependent manner and stimulated apoptosis of uterine fibroids cells by inducing caspase-3 activation, up-regulating Bim and down-regulating Bcl-2. Additionally, atorvastatin treatment suppressed phosphorylation of ERK1/2 and JNK. Furthermore, GGPP, a downstream lipid isoprenoid intermediate, significantly rescued the effect of atorvastatin. Conclusions: These results suggest that atorvastatin exerts anti-tumoral effects on uterine fibroids through inhibition of cell proliferation and induction of apoptosis in HMG-CoA-dependent pathway. Our results provide the first clinical and preclinical data on the use of atorvastatin as a promising nonsurgical treatment option for uterine fibroids.

Original languageEnglish (US)
Article number53
JournalJournal of Translational Medicine
Volume16
Issue number1
DOIs
StatePublished - Mar 9 2018

Keywords

  • Atorvastatin
  • HMG-CoA
  • MAPK
  • Uterine fibroids

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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