Different anticancer effects of fluvastatin on primary hepatocellular tumors and metastases in rats

Paragh, György; Fóris, Gabriella; Serés, I.; Karányi, Zsolt; Fülöp, Péter; Balogh, Zoltán; Kosztáczky, Béla; Teichmann, F; Kertai, P

doi:10.1016/j.canlet.2004.09.028

Cited by 24 publications

(19 citation statements)

References 14 publications

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“…First, the tumor types most susceptible to statin therapy have yet to be determined. Current preclinical and clinical data indicate that statins might be potentially useful for the treatment of melanoma [37], leukemia, brain cancer [38,39], hepatocellular cancer [124], and squamous cell cancer of the head and neck [43,59]. Second, it is not known which statins are most effective for cancer prevention and treatment.…”

Section: Resultsmentioning

confidence: 99%

The Role of Statins in Cancer Therapy

Cleeland²,

et al. 2006

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Learning ObjectivesAfter completing this course, the reader will be able to:1. Explain how statins, used in the treatment of hypercholesterolemia, may be applicable to cancer prevention.2. Discuss how statins potentially interfere with biologic processes relevant to cancer etiology. AbstractAdministration of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors, or statins, to ambulatory patients is associated with a lower incidence of long-term adverse cardiovascular events, including death, myocardial infarction, stroke, atrial fibrillation, and renal dysfunction. However, increasing clinical evidence suggests that statins, independent of their effects on serum cholesterol levels, may also play a potential role in the prevention and treatment of cancer. Specifically, statins have been shown to exert several beneficial antineoplastic properties, including decreased tumor growth, angiogenesis, and metastasis. The feasibility and efficacy of statins for the prevention and treatment of cancer is reviewed. The Oncologist 2006;11:306-315

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Section: Resultsmentioning

confidence: 99%

The Role of Statins in Cancer Therapy

Cleeland²,

et al. 2006

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“…Establishment of liver and kidney tumor cell lines from primary tumors. Chemical carcinogenesis was induced in newborn Fisher 344 inbred rats by Nnitrosodimethylamine [28]. Tumors were originally maintained by the orthotopic or heterotopic transplantation of tumor slices into rats.…”

Section: Metastatic Tumor Modelmentioning

confidence: 99%

Role of parathymic lymph nodes in metastatic tumor development

Bánfalvi

2011

Cancer Metastasis Rev

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Parathymic lymph nodes as potential sites of tumor progression have been neglected in humans. We have established a rat renal capsule-parathymic lymph node model to study in vivo metastasis. Epithelial liver carcinoma (HeDe) and mesenchymal mesoblastic nephroma (NeDe) cell lines have been established after inducing chemical carcinogenesis in newborn Fisher 344 inbred rats by N-nitrosodimethylamine. Implanting the exact number of tumor cells (HeDe, NeDe) under the renal capsule allowed the standardization and timing of metastatic development. Tumor cells released from the primary tumor in the peritoneal cavity were drained to the parathymic lymph nodes (PTNs) as sentinel lymph nodes. Similarly, tumor cells injected i.p. were engulfed by macrophages, drained through the transdiaphragmatic channels, and transported to the thoracal lymphatics, primarily to PTNs. Tumor cells after transdiaphragmic drainage can enter both anterior mammary and parathymic sentinel lymph nodes. The potential common origin can shed new light on the metastatic cell progression of PTNs and mammary tumors.

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“…Among them, a consistent association of decreased risk is found for hepatocellular carcinoma (HCC) and colorectal carcinoma (CRC; refs. [3][4][5][6]. Furthermore, experimental data have unveiled a beneficial effect of statins on these two important malignancies.…”

Section: Introductionmentioning

confidence: 99%

Inhibition of Autophagy Enhances Anticancer Effects of Atorvastatin in Digestive Malignancies

et al. 2010

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Preclinical and clinical studies have shown that statins, the 3-hydroxy-3-methylglutaryl-CoA reductase inhibitors with cholesterol-lowering properties, exhibited anticancer effects. However, the underlying mechanisms remain ill defined. In this study, we showed that atorvastatin could inhibit the growth of hepatocellular carcinoma (HCC) and colorectal carcinoma (CRC) cells via induction of apoptosis. Atorvastatin also induced autophagy that is a physiologic process involved in the turnover of intracellular organelles. Atorvastatin-induced autophagy was found to be inhibited by AMP-activated protein kinase (AMPK) small interfering RNA. Examination of HCC patients showed the positive correlation between AMPK activity and autophagic marker (beclin-1). Atorvastatin-induced AMPK activation could induce p21 expression, which was also positively correlated with beclin-1 expression in CRC patients. AMPK/p21 signaling caused endoplasmic reticulum (ER) stress response leading to the induction of autophagy. Inhibition of autophagy by an autophagic inhibitor bafilomycin A1 or genetic knockout of autophagy-related gene 5 enhanced atorvastatin-induced cytotoxicity and apoptosis. In summary, activation of AMPK by atorvastatin enhances p21 expression and ER stress response, leading to autophagy, which promotes survival of cancer cells. Combinations of atorvastatin with bafilomycin A1 provide a novel and promising strategy to improve the treatment of digestive malignancies.

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Different anticancer effects of fluvastatin on primary hepatocellular tumors and metastases in rats

Cited by 24 publications

References 14 publications

The Role of Statins in Cancer Therapy

The Role of Statins in Cancer Therapy

Role of parathymic lymph nodes in metastatic tumor development

Inhibition of Autophagy Enhances Anticancer Effects of Atorvastatin in Digestive Malignancies

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