Abstract
BackgroundMedical 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.MethodsInitially, 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.ResultsOur 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.ConclusionsThese 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.
Highlights
Medical therapeutic options remain quite limited for uterine fibroids treatment
Atorvastatin suppressed growth of uterine fibroids among patients with uterine fibroids and hyperlipidemia A total of 120 patients with uterine fibroids and hyperlipidemia were enrolled in this study
Our current study showed that atorvastatin inhibited proliferation and induced apoptosis in human uterine fibroids cells, and these effects could be reversed by adding GGPP, indicating the effects of atorvastatin on uterine fibroids growth depended on hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase
Summary
Medical therapeutic options remain quite limited for uterine fibroids treatment. Competitive inhibitors of 3-hydroxy-3-methylglutaryl-coenzyme A reductase, have anti-tumoral effects on multiple cancer types, little is known about their effects on uterine fibroids. Uterine fibroids are the most common benign tumors in women, with a lifetime incidence of approximately 70% [1, 2]. Statins exhibit multiple therapeutic effects in diverse tumors, limited work has been reported in uterine fibroids. Simvastatin inhibits proliferation and induces calcium-dependent apoptosis of human uterine fibroids cells in vitro and in vivo [18, 19]. For the first time to the best of our knowledge, that atorvastatin treatment exerts anti-neoplastic effects on uterine fibroids through inhibition of cell proliferation and induction of apoptosis in HMG-CoA-dependent pathway
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