Copyright ©The Author(s) 2020.
World J Clin Oncol. Aug 24, 2020; 11(8): 573-588
Published online Aug 24, 2020. doi: 10.5306/wjco.v11.i8.573
Table 1 In vitro studies on the anticancer potential of statins
Cancer typeCancer cell lineStatinObservationsChanges in intracellular signaling pathwaysRef.
HepatomaHepG2, Hep3BSimvastatinInhibition of cell growth in a dose- and time-dependent manner; G0/G1 cell cycle arrest; ApoptosisAMPK activation and STAT3/Skp2 axis suppression, inducing p21 and p27 accumulation[21]
Ovarian cancerHey, SKOV3AtorvastatinDose-dependent antiproliferative effect (1-250 µmol/L); Decrease in size and density of the cancer cells, and colony forming ability (at 150 µmol/L); G1-phase cell cycle arrest and S-phase decrease (at 150 µmol/L); Induction of apoptosis; Increased ROS levels in a dose-dependent manner; Induction of autophagy; Inhibition of cell adhesion and invasionInhibition of Akt/mTOR and activation of MAPK pathway; Decreased Mcl-1 expression, variable effect on Bcl-2 expression, increased cleaved PARP protein expression; Increased expression of cellular stress protein (PERK and Bip) (at 150 µmol/L); Reduced expression of VEGF protein and MMP-9[22]
Breast cancerSUM149, SUM159, MDA-MB-231SimvastatinInhibition of proliferation, decrease in S-phase and increase in G1/S-phase arrest; Suppression of cell migration; Decrease in tumor sphere formationDown-regulation of phosphorylated FOXO3a in SUM149 and SUM159 cells; Variable effect on total FOXO3a expression[43]
Endometrial cancerECC-1, Ishikawa, primary cultures of endometrial cancer cellsSimvastatinDose-dependent antiproliferative effect in both cancer cell lines (0.01-50 µmol/L), and in 5/8 primary cultures; G0/G1-phase cell cycle arrest, decreased S-phase in ECC-1 cells; Decreased HMG-CoA reductase activity; Induction of apoptosis; Increased DNA damage, cellular oxidative stress; Reduced cell adhesion and invasionInhibition of MAPK pathway, differential effects on the Akt/mTOR pathway; Increased cleaved caspase-3, decreased Bcl-2 expression, unmodified Mcl-1[20]
OsteosarcomaMNNG/HOSSimvastatinDose- and time-dependent antiproliferative effect (0.5-64 µmol/L); Dose-dependent morphological changes in treated cells: Cell shrinkage, loss of intercellular contact, reduced cell adherence, floating shapes; Dose-dependent suppression of cell migration, G0/G1-phase cell cycle arrest (16 µmol/L), and apoptosisDose-dependent down-regulation of MMP-2 and MMP-9; Down-regulation of cyclin D1, CDK2 and CDK4, up-regulation of CDKIs, p21 Cip1 and p27 Kip1; Decrease in PI3K and phospho-Akt expression, while total AKt remained unmodified, up-regulation of Bax and cleaved PARP expression, decreased Bcl-2 expression[44]
Lung adenocarcinomaA549, H1299, PC9, HCC827, H1975, H1435, PE8sc, CL1-0, Bm7, and immortalized normal lung epithelial cells (HBEC3KT)SimvastatinHigher cytotoxicity against LC cells with p53 mutation; Dose-dependent apoptosis; Reduced lipid rafts in mutant p53-bearing LC cells; Reduction in the migration distance; Promotes the nuclear transport of mutant p53 in Bm7 and H1435 cellsIncreased levels of cleaved PARP and cleaved caspase-3; No difference in the level of LC3-II; Decreased level of p53, and increased level of high molecular weight HSP-40[45]
Table 2 A summary of recent meta-analyses evaluating the benefits of statins in various types of cancer
Cancer typeNo. of clinical trials and subjects includedObjectiveResultsRef.
Active cancerTen studies, 1881 individuals with stage 3 or higher diseaseTo evaluate the randomized controlled trials of statins in addition to standard anticancer therapyThe addition of statins to standard anticancer therapy did not improve overall survival or progression-free survival[105]
Solid cancerEight randomized controlled trials, 1760 patientsTo evaluate the effect of statins added to systemic anticancer therapy in patients with solid cancerThe addition of statins to chemotherapy did not significantly increase the incidence of grade 3-5 adverse events, did not improve the overall response rate and failed to prolong the progression-free survival and overall survival compared with that of chemotherapy alone[106]
Pancreatic cancerSix retrospective cohort studies, 12057 patients were includedTo explore the association between statin and metformin use and overall survival of pancreatic cancer patientsStatin use was associated with a significantly improved overall survival (but with a significant publication bias)[107]
Twenty-six studies, more than 3 million participants, 170000 pancreatic cancer patientsThe relationship between statin use and the risk of pancreatic cancerStatins have a protective effect on pancreatic cancer[108]
Kidney cancerTwelve studies, 18105 patientsTo evaluate the association between statin use and kidney cancer survival outcomesStatin use was not associated with significant recurrence-free survival or progression-free survival; statin use was associated with marked improvements in cancer-specific survival and overall survival[109]
Lung cancerSeventeen studies, 98445 patientsTo analyze the impact of statins on mortality and survival of LC patientsStatins were potentially associated with a decreased risk of mortality and an improvement of overall survival in observational studies but not in randomized controlled trials; Statins potentially enhanced the effects of tyrosine kinase inhibitors and chemotherapy on the overall survival of patients with non-small cell LC[110]