When activated by the agonistic Fas

antibody 7C11, this r

When activated by the agonistic Fas

antibody 7C11, this receptor produces apoptosis. After activation of SSTRs either by the endogenous agonist or Oct, we were unable to detect any enhancement of Fas-induced apoptosis. This is in contrast with previous data obtained in the pancreatic cancer BxPC-3 cells [50]. Indeed, SSTR2 was shown to up-regulate TNF-related apoptosis-inducing ligand (TRAIL) receptors, DR4 and TNFRI that www.selleckchem.com/products/gm6001.html trigger death first, by activating caspase 8 and second by down-regulating the anti-apoptotic mitochondrial protein Bcl2. Opioid receptors are also expressed in https://www.selleckchem.com/products/gsk3326595-epz015938.html immune cells [51] in which they promote apoptosis by regulating Fas expression [31]. These GPCRs were shown to heterodimerize with SSTRs [52] and we hypothesized that co-treatment with opioids and Sst or Oct would activate signalling pathways leading to apoptosis. In the current study, we demonstrated by molecular experiments and western blot that U266 cells express MOP-R that are able to bind a prototypical ligand [3H]diprenorphine. When morphine (a MOP-R “”selective”" agonist) was used alone, no evidence for apoptosis was detected. Similar results were obtained when both opioid and somatostatin receptors were co-activated. While morphine and ethylketocyclazocine were reported to interact with SSTRs in the opposum kidney cells and HepG2 cell line, respectively, and promote cell growth inhibition [53, 54], our data rule out such conclusions in

our cellular model. Conclusion In conclusion, we demonstrated

that the human MM cell line U266 expresses both SSTRs and the MOP-R. However, their stimulation by Sst, Oct or morphine alone or in combination Selleckchem CBL0137 fails to induce cell cycle modifications and apoptosis in U266 cells. While we demonstrated that Oct has no effect on the myeloma cell lines U266 and LP-1 (data not shown), we can not exclude that such targeted treatment would be ineffective in patients. Authors’ information CK: Ph.D. student. In addition CK is a recipient of the Ministère de l’enseignement supérieur et de la recherche TC: M.D. student BS: Ph.D. PJ: M.D., Ph. D. SA: Ph.D. Acknowledgements We thank la Ligue contre le cancer, comité de l’Orne for their financial support, Mrs Maryline Duval and Dr Laurent Poulain (Grecan, Immune system Centre François Baclesse, Caen, France), Drs Mikael Roussel and Véronique Salaün (laboratoire d’hématologie, Centre Hospitalier et Universitaire de Caen, France) for their advices concerning flow cytometry. References 1. Yasui H, Hideshima T, Richardson PG, Anderson KC: Novel therapeutic strategies targeting growth factor signalling cascades in multiple myeloma. Br J Haematol 2006, 132 (4) : 385–397.PubMed 2. Rajkumar SV, Gertz MA, Kyle RA, Greipp PR: Current therapy for multiple myeloma. Mayo Clin Proc 2002, 77 (8) : 813–822.CrossRefPubMed 3. Hideshima T, Anderson KC: Molecular mechanisms of novel therapeutic approaches for multiple myeloma. Nat Rev Cancer 2002, 2 (12) : 927–937.CrossRefPubMed 4.

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