The role of atorvastatin in suppressing tumor growth of uterine fibroids

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.

Targeting IL‐10, ZO‐1 gene expression and IL‐6/STAT‐3 trans‐signaling by a combination of atorvastatin and mesalazine to enhance anti‐inflammatory effects and attenuates progression of oxazolone‐induced colitis

“…In contrast to our finding, Shen et al & Chen et al reported that atorvastatin treatment increases caspase‐3 levels [68,69]. Chen et al [68] demonstrated that atorvastatin significantly inhibited growth and induced apoptosis in human prostate cancer cells by inhibition of caspase‐3 activity.…”

“…Chen et al [68] demonstrated that atorvastatin significantly inhibited growth and induced apoptosis in human prostate cancer cells by inhibition of caspase‐3 activity. Also, Shen et al [69] suggested that atorvastatin exerted anti‐tumor effects on uterine fibroids through induction of apoptosis in HMG‐CoA‐dependent pathway.…”

Proteome and phosphoproteome reveal mechanisms of action of atorvastatin against esophageal squamous cell carcinoma

“…Myalgia is the most common adverse reaction of atorvastatin [16]. Recent studies have suggested that atorvastatin also had anti-tumor properties and these studies have mainly focused on a relationship between cholesterol biosynthesis and cancer [17]. Some plausible mechanism for atorvastatin against cancer have also been reported.…”

Use of 20mg statins (atorvastatin/simvastatin) as a novel new option of medically treating fibroids–overcoming the drawback of selective progesterone receptor modulators of interruption before long term use

“…Moreover GGPP, a downstream lipid isoprenoid intermediate significantly rescued the effects of atorvastatin and claimed the 1st clinical as well as preclinical data on use of atorvastatin as a promising nonsurgical method for treating uterine fibroids. 11 As per Bjorkhem-Bergman et al, 12 there was a large difference between the statin concentrations used in cells in vitro experiments and those found in human plasma. They reported pharmacokinetic data that 40mg of simvastatin produces a mean serum concentration of 2.2-4.3nM and the highest concentration of 19-31nM, although its pleiotropic effect is examined in vitro using micromolar concentrations.…”