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Cancer & Metabolism
Published in: Cancer & Metabolism 1/2018

Open Access 01-12-2018 | Rapid communication

Elevated circulatory levels of leptin and resistin impair therapeutic efficacy of dacarbazine in melanoma under obese state

Authors: Parmanand Malvi, Balkrishna Chaube, Shivendra Vikram Singh, Naoshad Mohammad, Maleppillil Vavachan Vijayakumar, Snahlata Singh, Surbhi Chouhan, Manoj Kumar Bhat

Published in: Cancer & Metabolism | Issue 1/2018

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Abstract

Background

Obesity is associated with increased risk, poor prognosis and outcome of therapy, in various cancers. Obesity-associated factors or adipokines, especially leptin and resistin, are purported to promote growth, survival, proliferation, and invasiveness of cancer cells. However, the mechanistic link between these adipokines and therapeutic response in malignancies is not clearly understood.

Methods

ob/ob and db/db mouse models were used in this study to evaluate the role of leptin and resistin towards the outcome of dacarbazine (DTIC) therapy in melanoma. Unique in vitro approaches were employed to complement in vivo findings by culturing melanoma cells in the serum collected from the experimental mice.

Results

Here, we have shown the role of important adipokines leptin and resistin in growth and the outcome of DTIC therapy in melanoma. Both leptin and resistin not only enhance proliferation of melanoma cells but also are involved in impairing the therapeutic efficacy of DTIC. Leptin and resistin treatment caused an increase in the protein levels of fatty acid synthase (FASN) and caveolin 1 (Cav-1) respectively, through their stabilization in A375 cells. Further, it was observed that leptin and resistin impaired the response of melanoma cells to DTIC via upregulation of heat shock protein 90 (Hsp90) and P-glycoprotein (P-gp) respectively.

Conclusion

These findings unraveled the involvement of adipokines (leptin and resistin) in melanoma progression, and more importantly, in the outcome of DTIC therapy.
Appendix
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Metadata
Title
Elevated circulatory levels of leptin and resistin impair therapeutic efficacy of dacarbazine in melanoma under obese state
Authors
Parmanand Malvi
Balkrishna Chaube
Shivendra Vikram Singh
Naoshad Mohammad
Maleppillil Vavachan Vijayakumar
Snahlata Singh
Surbhi Chouhan
Manoj Kumar Bhat
Publication date
01-12-2018
Publisher
BioMed Central
Published in
Cancer & Metabolism / Issue 1/2018
Electronic ISSN: 2049-3002
DOI
https://doi.org/10.1186/s40170-018-0176-5

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