Immunohistochemical and histomorphological analysis of rat mammary tumors after simvastatin treatment

Kubatka, Peter; Kajo, Karol; Žihlavníková, Katarína; Adamicová, Katarína; Výbohová, Desanka; Péč, Martin; Nosáľ, Vladimír; Stollárová, Nadežda; Bojková, Bianka; Kassayová, Monika; Orendáš, Peter

doi:10.4149/neo_2012_066

Cited by 18 publications

(11 citation statements)

References 27 publications

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“…In our previous study a decrease in Ki67 protein expression by 27% in simvastatin‐treated rat mammary tumour cells was found (Kubatka et al . ). However, the tumour cell expression of Ki67 was not changed after fluvastatin administration in the same model (Kubatka et al .…”

Section: Discussionmentioning

confidence: 97%

“…On the other hand, significant anti‐tumour effects of dietary administered lipophilic statins (atorvastatin, simvastatin and fluvastatin) in the chemoprevention of rat mammary carcinogenesis in our previous studies were observed (Kubatka et al . , , ). In our recent experiment, hydrophilic rosuvastatin (250 mg/kg) has shown lower non‐significant anti‐neoplastic activity than lipophilic statins in this model of experimental breast cancer (Kubatka et al .…”

Section: Discussionmentioning

confidence: 99%

“…) and pro‐apoptotic shift in Bcl‐2/Bax protein expression after simvastatin treatment (Kubatka et al . ) were observed. However, our recent results did not suggest clear pro‐apoptotic effects of fluvastatin in rat mammary carcinomas (Kubatka et al .…”

mentioning

confidence: 86%

“…In our recent experiments a significant chemopreventive effect of simvastatin in rat mammary carcinogenesis was accompanied by distinct decrease in the expression of the proliferating cell nuclear antigen Ki67 (Kubatka et al . ). Proposed mechanisms for statin‐mediated apoptosis include an upregulation of pro‐apoptotic protein expression (Bax, Bim) together with decreased anti‐apoptotic protein expression (Bcl‐2) (Yu et al .…”

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confidence: 97%

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Melatonin potentiates the anti‐tumour effect of pravastatin in rat mammary gland carcinoma model

Orendáš

Kubatka

Bojková

et al. 2014

Int J Experimental Path

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Previous studies in the field of cancer research have suggested a possible role for statins in the reduction of risk in certain malignancies. The purpose of these studies was to examine the chemopreventive effects of pravastatin alone and in combination with pineal hormone melatonin in the N-methyl-N-nitrosourea-induced mammary carcinogenesis model. Pravastatin was given orally (1 00 mg/kg) and melatonin was added to the water (20 μg/ml). Chemoprevention began seven days prior to carcinogen administration and subsequently continued for 15 weeks until autopsy. At autopsy, mammary tumours were removed and prepared for histopathological and immunohistochemical analysis. Parameters of experimental carcinogenesis, mechanism of action (biomarkers of apoptosis, angiogenesis and proliferation) and side effects after long-term treatment in animals were assessed. Pravastatin alone suppressed tumour frequency by 20.5% and average tumour volume by 15% compared with controls. Combined administration of the drugs decreased tumour frequency by 69% and lengthened tumour latency by nine days compared with control animals. The ration between high and low grade carcinomas was apparently reduced in both treated groups. The analysis of carcinoma cells showed significant expression increase in caspase-3 and caspase-7 after pravastatin treatment; however, combined treatment even more pronounced increase in the expression of both caspases. Regarding VEGFR-2 expression, a small effect in carcinomas of both treated groups was found. In plasma metabolism evaluation, pravastatin alone significantly decreased levels of glucose and triacylglycerols. Our results suggest a mild anti-neoplastic effect of pravastatin in this rat mammary gland carcinoma model. Statins co-administered with other suitable drug (e.g. melatonin) should be further evaluated for tumour-preventive properties.

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Section: Discussionmentioning

confidence: 97%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 86%

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confidence: 97%

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Melatonin potentiates the anti‐tumour effect of pravastatin in rat mammary gland carcinoma model

Orendáš

Kubatka

Bojková

et al. 2014

Int J Experimental Path

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“…Ezek a fehérjék a Ras/Raf/MEK/ ERK jelátviteli kaszkádra hatnak, amely a sejtosztódást serkenti [5]. Simvastatinnal kezelt patkányokban a Bcl-2/Bax protein arány proapoptotikus irányba billen, és ez a magas gradusú emlőcarcinoma-sejteket alacsony gradusúvá alakítja [6]. A lovastatin egerekben csökkentette a dohányzás indukálta tüdőadenomák többgócúságát, de ezek méretére és előfordulására nem volt befolyással [7].…”

Section: A Statinok Tumorképződésre Gyakorolt Hatásai áLlatkísérletekbenunclassified

Statins and gastrointestinal cancers

et al. 2014

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A statinok tumorképződésre gyakorolt gátlóhatása állatkísérletekben és humán daganatsejtvonalakkal végzett vizsgá-latok során többféle emésztőrendszeri tumor esetében is igazolódott. A statinok kemopreventív hatásmechanizmusa még nem teljesen tisztázott, de a megnövekedett oxidatív stressz, a fokozott autofágia, a pro-és antiproliferatív fehérjék expressziójának megváltozása és a sejten belüli jelátviteli útvonalak befolyásolása szerepet játszik. A nagy esetszámú, randomizált klinikai tanulmányok egyelőre nem igazolták a kísérletes adatok alapján várt eredményeket. Jelen összefoglaló célja, hogy bemutassa a statinok kemopreventív szerepéről eddig megjelent irodalmi adatokat az egyes emésztőrendszeri daganatok vonatkozásában. A klinikai vizsgálatok eredményei alapján elmondható, hogy 10-20 mg/nap dózisú statin esetén nem vagy csak minimális tumorprotektív hatás észlelhető. Hidrofi l statinok esetén nincs, hidrofób statinoknál azonban szignifi káns a kemopreventív hatás. 30-40 mg/nap dózisban történő, hosszan tartó szedés hatásairól kevés adat áll rendelkezésre. A statinok hatásának hosszú távú vizsgálata -vegyülettípus és dózis szerint alcsoport-analízist végezve -valamennyi emésztőrendszeri daganat esetében szükséges a későbbiekben. A statinokkal történő kemoprevenció nem része a mindennapi orvosi gyakorlatnak. A statinok kemopreventív céllal történő alkalmazása nem helyettesítheti a rendszeres onkológiai szűrést és követést. Orv. Hetil., 2014, 155(18), 687-693. Kulcsszavak: statin, kemoprevenció, emésztőrendszeri daganatok Statins and gastrointestinal cancersThe antitumour effect of statins has already been proven in animal experiments and human cancer cell lines in several gastrointestinal cancers. The chemopreventive mechanism is not completely clarifi ed but the enhancement of oxidative stress, increased autophagy, altered expression of pro-and antiproliferative proteins and their infl uence on intracellular signaling pathways may play a role. Randomized studies, however, failed to confi rme the expected results obtained from experimental studies. The goal of this review is to summarize the data available in the literature regarding the chemopreventive effects of statins on several gastrointestinal cancers. Results of clinical trials suggest that 10-20 mg statin daily has no or minimal antitumour effect. Chemopreventive effect of hydrophilic statins could not be detected but it seems to be signifi cant in the case of hydrophobic statins. There are only few data available on the long-term daily use of 30-40 mg statins. Further long-term evaluation of the effect of statins regarding gastrointestinal cancers is needed, and an analysis of compound-and dose-related subgroups would be benefi cial. Chemoprevention with statins cannot yet be accepted as standard medical practice. Use of statins as chemopreventive agents cannot be a substitute for regular oncological screening or surveillance.

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Risk-Reducing (Chemopreventive) Agents in Breast Cancer Prevention

Gronich

Rennert

2016

Trends in Breast Cancer Prevention

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Immunohistochemical and histomorphological analysis of rat mammary tumors after simvastatin treatment

Cited by 18 publications

References 27 publications

Melatonin potentiates the anti‐tumour effect of pravastatin in rat mammary gland carcinoma model

Melatonin potentiates the anti‐tumour effect of pravastatin in rat mammary gland carcinoma model

Statins and gastrointestinal cancers

Risk-Reducing (Chemopreventive) Agents in Breast Cancer Prevention

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