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High level interleukin-6 in the medium of human pancreatic cancer cell culture suppresses production of neurotransmitters by PC12 cell line

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Abstract

It has been suggested that pancreatic cancer is associated with a greater prevalence of depression than many other cancers, but the mechanism accounting for this potential association has not yet been illustrated. In the present study, conditioned media (CM) from three pancreatic cancer cell lines and primary pancreatic cancer cells from two patients were added to culture system of differentiated pheochromocytoma cell line PC12. The release of dopamine (DA) and norepinephrine (NE) by PC12 was significantly inhibited after CM treatment (P < 0.05), similar to what happened after recombinant interleukin 6(IL-6) treatment. Furthermore, pretreatment with anti-IL-6 antibody significantly blocked the inhibitory effects of pancreatic cancer CM on DA and NE production (P < 0.05). We also demonstrated that tyrosine hydroxylase (TH), the rate-limiting enzyme for synthesis of catecholamine, was reduced after exposure to IL-6, which was accompanied by JAK-STAT3 pathway activation. Our results demonstrated that IL-6 in CM from pancreatic cancer down-regulated the production of DA and NE by PC12 cell. The possible underlying mechanisms might be decreasing TH production via activation of JAK-STAT3 signal transduction pathway. The present study might help to better understand the close relationship between pancreatic cancer and depression.

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Acknowledgments

This study was supported by the PHD finance conduct.

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All authors report no biomedical financial interests or potential conflicts of interest.

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Authors and Affiliations

  1. Department of Hematology, Chang Zheng Hospital, Second Military Medical University, Shanghai, 200003, China

    Rong Li & Jian Hou

  2. Department of Oncology, The Tenth People’s Hospital of Shanghai, Tongji University, Shanghai, 200321, China

    Qing Xu

  3. Department of Genetic Engineering Development, Shanghai Fudan-Zhangjiang Bio-pharmaceutical Co., Ltd., Shanghai, 200423, China

    Qing-Jun Liu & Yi-Jun Shen

  4. Department of Psychosocial Oncology and Palliative Care, Princess Margaret Hospital, 610 University Avenue, Toronto, ON, M5G 2M9, Canada

    Gary Rodin & Madeline Li

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  1. Rong Li
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  2. Jian Hou
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Correspondence to Jian Hou.

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Li, R., Hou, J., Xu, Q. et al. High level interleukin-6 in the medium of human pancreatic cancer cell culture suppresses production of neurotransmitters by PC12 cell line. Metab Brain Dis 27, 91–100 (2012). https://doi.org/10.1007/s11011-011-9270-x

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  • DOI: https://doi.org/10.1007/s11011-011-9270-x

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