Metabotropic glutamate receptor 5 mediates the suppressive effect of 6-OHDA-induced model of Parkinson’s disease on liver cancer
6-OHDA-lesioned MN9D cells suppressed the growth and migration of Hepa1-6 cells via the down-regulation of mGluR5-mediated ERK and AKT pathway. [Display omitted] Numerous epidemiological studies suggested that there is a variable cancer risk in patients with Parkinson’s disease (PD). However, the un...
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Published in: | Pharmacological research 2017-07, Vol.121, p.145-157 |
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Main Authors: | , , , , , , , |
Format: | Article |
Language: | eng |
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Online Access: | Get full text |
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Summary: | 6-OHDA-lesioned MN9D cells suppressed the growth and migration of Hepa1-6 cells via the down-regulation of mGluR5-mediated ERK and AKT pathway.
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Numerous epidemiological studies suggested that there is a variable cancer risk in patients with Parkinson’s disease (PD). However, the underlying mechanisms remain unclear. In the present study, the role of metabotropic glutamate receptor 5 (mGluR5) has been investigated in 6-hydroxydopamine (6-OHDA)-induced PD combined with liver cancer both in vitro and in vivo. We found that PD cellular model from 6-OHDA-lesioned MN9D cells suppressed the growth, migration, and invasion of Hepa1-6 cells via down-regulation of mGluR5-mediated ERK and Akt pathway. The application of 2-methyl-6-(phenylethyl)-pyridine and knockdown of mGluR5 further decreased the effect on Hepa-1-6 cells when co-cultured with conditioned media. The effect was increased by (S)-3,5-dihydroxyphenylglycine and overexpression of mGluR5. Moreover, more release of glutamate from 6-OHDA-lesioned MN9D cells suppressed mGluR5-mediated effect of Hepa1-6 cells. Application of riluzole eliminated the increased glutamate release induced by 6-OHDA in MN9D cells and aggravated the suppressive effect on Hepa-1-6 cells. In addition, the growth of implanted liver cancer was inhibited in 6-OHDA induced PD-like rats, and was associated with increased glutamate release in the serum and down-regulation of mGluR5 in tumor tissue. Collectively, these results indicate that selective antagonism of glutamate and mGluR5 has a potentially beneficial effect in both liver cancer and PD, and thus may provide more understanding for the clinical investigation and further an additional therapeutic target for these two diseases. |
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ISSN: | 1043-6618 1096-1186 |