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Leptin enhances N-methyl-N’-nitro-N-nitrosoguanidine (MNNG)-induced tumour growth in gastric mucosa of male Sprague-Dawley rats

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Abstract

Individuals who are obese are at a greater risk of developing gastric cancer. They are however also hyperleptinaemic. Chronic leptin treatment has been shown to upregulate numerous cancer-causing genes in the stomach of male Sprague-Dawley rats. It is however unclear if leptin enhances the effect of gastric carcinogens in vivo. This study was therefore done to investigate the effect of leptin on gastric carcinogenesis in rats treated with N-methyl-N’-nitro-N-nitrosoguanidine (MNNG). Twenty-four, 6-week old male Sprague-Dawley rats were divided equally into three groups: G1 served as age-matched controls; G2 was treated with MNNG in drinking water ad libitum (200 mg L−1); G3 was given leptin and MNNG. Rats were euthanized after 40 weeks of treatment and their stomachs were removed for histopathology, microarray, and RT-qPCR analysis. Fisher’s exact test and one-way ANOVA were used to analyse the data. Fifty percent of the MNNG-treated rats developed gastric hyperplasia (p < 0.05), but there was no significant change in any carcinogenic genes. Concurrent MNNG and leptin treatment however induced hyperplasia, dysplasia, hypertrophy, and adenocarcinoma in 75% (6/8) of the rats; with upregulation of microRNAs, olfactory receptors, Hey2 (transcription factor), Tmed2 (vesicular trafficking), and Lcn11 (cell proliferation) genes. It appears that leptin enhances MNNG- induced tumour growth in stomachs of Sprague-Dawley rats and its role in gastric cancer requires further scrutiny.

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Acknowledgements

The authors wish to acknowledge the staff of Laboratory Animal Care Unit (LACU) and Institute of Medical Molecular Biotechnology (IMMB) for their technical help and support.

Funding

This study was supported by 600-IRMI/MyRA 5/3/GIP (019/2017) Research Grant.

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Authors and Affiliations

  1. Faculty of Medicine, Asia Metropolitan University, 81750, Masai, Johor, Malaysia

    Faizatul Isyraqiah

  2. Faculty of Medicine, Lincoln University College, 47301, Petaling Jaya, Selangor, Malaysia

    Methil Kannan Kutty

  3. Faculty of Medicine, Universiti Teknologi MARA, 47000, Sungai Buloh, Selangor, Malaysia

    Damayanthi Durairajanayagam & Harbindar Jeet Singh

  4. I-PPerFORM, Universiti Teknologi MARA, 47000, Sungai Buloh, Selangor, Malaysia

    Harbindar Jeet Singh

Authors
  1. Faizatul Isyraqiah
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  2. Methil Kannan Kutty
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  3. Damayanthi Durairajanayagam
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  4. Harbindar Jeet Singh
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Contributions

FI conducted the experiments, analysed the data, interpreted the results, and wrote the manuscript; MKK participated in the study design, analysed histology slides and microarray data, helped in the preparation of the manuscript and reviewed the manuscript; DD interpreted the results and reviewed the manuscript; HJS participated in the study design, provided the overall supervision, interpreted the results, helped in the preparation of the manuscript and reviewed the manuscript.

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Correspondence to Harbindar Jeet Singh.

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Isyraqiah, F., Kutty, M.K., Durairajanayagam, D. et al. Leptin enhances N-methyl-N’-nitro-N-nitrosoguanidine (MNNG)-induced tumour growth in gastric mucosa of male Sprague-Dawley rats. Mol Biol Rep 46, 5967–5975 (2019). https://doi.org/10.1007/s11033-019-05030-z

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  • DOI: https://doi.org/10.1007/s11033-019-05030-z

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