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Insulin Prevents Leptin Inhibition of RM1 Prostate Cancer Cell Growth

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Pathology & Oncology Research

Abstract

The association between obesity and cancer is controversial: whereas several epidemiological, clinical and research studies using cancer cell lines have supported that high levels of insulin and leptin could favor prostate cancer development and dissemination, other studies have demonstrated opposite effects or even absence of association. The main goal of this study was to evaluate the in vitro proliferation of murine androgen insensitive prostate carcinoma cells RM1 in the presence of leptin and insulin. After assessing and confirming the presence of leptin and insulin receptors in RM1 cells by immunocytochemistry, cells were cultured in the presence of different concentrations of leptin (0, 25, 50, 100 and 200 ng/mL), insulin (0, 50, 100, 150 and 200 nM) or leptin plus insulin ( 25 ng/ml + 50 nM; 50 ng/ml + 100 nM; 100 ng/ml + 150 nM; 200 ng/ml + 200 nM; 25 ng/ml + 150 nM; 100 ng/ml + 50 nM of leptin plus insulin, respectively). Cell proliferation was evaluated by assessing the percentage of resazurin reduction, a surrogate marker of cell metabolic rate. Leptin significantly decreased the percentage of resazurin reduction in all studied concentrations while there was only a slight or non significant difference in RM1cell proliferation in the presence of insulin or insulin combined with leptin when compared with control. These results show that leptin decreases RM1 prostate cancer cell proliferation at the studied concentrations, while insulin is able to antagonize the leptin inhibition of RM1 prostate cancer cell growth in vitro. The difference in cell growth that is modulated by the various hormonal environments may explain the heterogeneous behavior of prostate cancer in the obese human population.

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Abbreviations

ICC:

Immunocytochemistry

TNF-α:

Tumor necrosis factor

IL-6:

Interleucine-6

VEGF:

Endothelial vascular growing factor

ObR:

Leptin receptor

ObRa:

Leptin receptor short isoform

ObRb:

Leptin receptor long isoform

Ras/ERK1/2:

Ras/extracellular signal – regulated kinases 1/2

JAK2 / STAT3:

Janus kinase 2 / signal transducer and activator of transcription 3

PI-3K / Akt / GSK 3:

Phosphoinositite 3 kinase / protein kinase B / glycogen synthesis kinase 3

RAS/RAF/MEK/ERK:

Ras/Raf/ mitogen-activated protein kinase/ extracellular-signal-regulated kinase pathway

Akt/PI-3K:

Protein kinase B/Phosphatidylinositol 3-kinases

IGF-1:

Insulin-like growth factor-1

DIO:

Diet induced obesity mice

SEM:

Standard error of the mean

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Acknowledgment

We thank Prof Thompson from MD Anderson Cancer Center for kindly providing the RM1 cells that made this work possible; Rui Medeiros, Ricardo Ribeiro for support with cell culture.

UMIB is funded by grants from Foundation for Science and Technology (FCT) POCTI/FEDER Portugal.

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Authors and Affiliations

  1. Department of Anatomy and UMIB (Unit for Multidisciplinary Biomedical Research) of ICBAS, University of Porto, 4099-003, Porto, Portugal

    Andreia M. Ribeiro, Sofia Pereira, Sara Andrade, Madalena Costa, Artur P. Aguas & Mariana P. Monteiro

  2. Department of Pathology and Immunology of ICBAS, University of Porto, 4099-003, Porto, Portugal

    Carlos Lopes

  3. Department of Anatomy and UMIB - ICBAS, Instituto de Ciências Biomédicas Abel Salazar, University of Porto, Largo Prof.Abel Salazar, 4099-003, Porto, Portugal

    Mariana P. Monteiro

Authors
  1. Andreia M. Ribeiro
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  2. Sofia Pereira
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  3. Sara Andrade
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  4. Madalena Costa
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  5. Carlos Lopes
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  7. Mariana P. Monteiro
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Correspondence to Mariana P. Monteiro.

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Ribeiro, A.M., Pereira, S., Andrade, S. et al. Insulin Prevents Leptin Inhibition of RM1 Prostate Cancer Cell Growth. Pathol. Oncol. Res. 18, 499–507 (2012). https://doi.org/10.1007/s12253-011-9473-9

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  • DOI: https://doi.org/10.1007/s12253-011-9473-9

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