A novel therapeutic approach to colorectal cancer in diabetes: role of metformin and rapamycin
| Autor: | Liliane Massaad-Massade, Angelo Leone, Alice Gerges Geagea, Céline Gracia, Assaad A. Eid, Sahar Al Kattar, Manfredi Rizzo, Francesco Cappello, Giovanni Tomasello, Abdo Jurjus |
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| Přispěvatelé: | Università degli studi di Palermo - University of Palermo, Department of Experimental Medicine and Clinical Neurosciences (BioNeC), Institut Gilbert-Laustriat : Biomolécules, Biotechnologie, Innovation Thérapeutique, Université Louis Pasteur - Strasbourg I-Centre National de la Recherche Scientifique (CNRS), MASSADE, Liliane, Geagea,AG, Rizzo,M, Jurjus,A, Cappello,F, Leone,A, Tomasello,G, Gracia,C, Al Kattar,S, Massaad-Massade,L, Eid,A |
| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Combination therapy Colorectal cancer inflammatory cytokines Settore BIO/11 - Biologia Molecolare Inflammation colorectal cancer [SDV.CAN]Life Sciences [q-bio]/Cancer Pharmacology Proinflammatory cytokine 03 medical and health sciences 0302 clinical medicine [SDV.CAN] Life Sciences [q-bio]/Cancer Diabetes mellitus colorectal cancer biabetes therapeutic approach Medicine PI3K/AKT/mTOR pathway business.industry Correction medicine.disease 3. Good health Metformin Settore MED/18 - Chirurgia Generale 030104 developmental biology Oncology probiotics 030220 oncology & carcinogenesis diabetes mellitus mTOR Tumor necrosis factor alpha medicine.symptom business medicine.drug Research Paper |
| Zdroj: | Oncotarget Oncotarget, Impact journals, 2019 Scopus-Elsevier |
| ISSN: | 1949-2553 |
| Popis: | International audience; The link between colorectal cancer (CRC), diabetes mellitus (DM) and inflammation is well established, and polytherapy, including rapamycin, has been adopted. This study is a novel approach that aimed at assessing the effect of a combination therapy of metformin and rapamycin on the control or prevention of CRC in diabetic animals, in presence or absence of probiotics. Fifty NOD/SCIDs male mice developed xenograft by inoculating HCT116 cells. They were equally divided into diabetics (induced by Streptozotocin) and non-diabetics. Metformin was given in drinking water, whereas rapamycin was administered via intra-peritoneal injections. Probiotics were added to the double therapy two weeks before the sacrifice. Assessment was performed by clinical observation, histological analysis, Reactive oxygen species (ROS) activities and molecular analysis of Interleukin 3 and 6, Tumor Necrosis Factor alpha, AMP-activated protein Kinase and the mammalian target of rapamycin. Decreases in the level of tumorigenesis resulted, to various extents, with the different treatment regimens. The combination of rapamycin and metformin had no significant result, however, after adding probiotics to the combination, there was a marked delay in tumor formation and reduction of its size, suppression of ROS and a decrease in inflammatory cytokines as well as an inhibition of phosphorylated mTOR. Existing evidence clearly supports the use of rapamycin and metformin especially in the presence of probiotics. It also highlighted the possible mechanism of action of the 2 drugs through AMPK and mTOR signaling pathways and offered preliminary data on the significant role of probiotics in the combination. Further investigation to clarify the exact role of probiotics and decipher in more details the involved pathways is needed. |
| Databáze: | OpenAIRE |
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