Abstract The link between colorectal cancer (CRC), diabetes mellitus (DM) and inflammation is well established, and polytherapy, including rapamycin, has been commonly adopted. However, due to the relatively weak response of CRC to rapamycin, combination with other molecules including metformin has become a potentially promising approach. 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 colorectal cancer in diabetic animals, in presence or absence of probiotics. Fifty NOD/SCIDs male mice developed xenograft by inoculating HCT116 cells into the flank; they were equally divided into diabetics (induced by STZ) and non-diabetics. Metformin was given in drinking water, whereas rapamycin was administered via i.p injections. Probiotics were added to the double therapy two weeks before the sacrifice. Assessment was performed by clinical observation, gross anatomic inspection of abdominal organs, histological analysis, mast cells and ROS activities determination, as well as, by molecular analysis of pro-inflammatory cytokines (IL- 3, IL-6 and TNF), AMPK and mTOR. A decrease in the level of tumorigenesis resulted, to various extents, with the different treatment regimens. The combination of rapamycin and metformin had no significant added effect, however, when probiotics were added 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 p-mTOR. Existing evidence clearly supports the use of rapamycin and metformin especially in the presence of probiotics. There is an immunomodulatory effect of probiotics in colorectal carcinogenesis. This study confirmed some of the effects observed in several studies and clinical trials. It also described 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. However, the application of probiotics in CRC still needs further investigation aiming to clarify its exact role and decipher in more details the involved pathways. Key words: CRC, DM, Probiotics, Inflammatory Cytokines, AMPK, mTOR, ROS.

Abstract The link between colorectal cancer (CRC), diabetes mellitus (DM) and inflammation is well established, and polytherapy, including rapamycin, has been commonly adopted. However, due to the relatively weak response of CRC to rapamycin, combination with other molecules including metformin has become a potentially promising approach. 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 colorectal cancer in diabetic animals, in presence or absence of probiotics. Fifty NOD/SCIDs male mice developed xenograft by inoculating HCT116 cells into the flank; they were equally divided into diabetics (induced by STZ) and non-diabetics. Metformin was given in drinking water, whereas rapamycin was administered via i.p injections. Probiotics were added to the double therapy two weeks before the sacrifice. Assessment was performed by clinical observation, gross anatomic inspection of abdominal organs, histological analysis, mast cells and ROS activities determination, as well as, by molecular analysis of pro-inflammatory cytokines (IL- 3, IL-6 and TNF), AMPK and mTOR. A decrease in the level of tumorigenesis resulted, to various extents, with the different treatment regimens. The combination of rapamycin and metformin had no significant added effect, however, when probiotics were added 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 p-mTOR. Existing evidence clearly supports the use of rapamycin and metformin especially in the presence of probiotics. There is an immunomodulatory effect of probiotics in colorectal carcinogenesis. This study confirmed some of the effects observed in several studies and clinical trials. It also described 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. However, the application of probiotics in CRC still needs further investigation aiming to clarify its exact role and decipher in more details the involved pathways. Key words: CRC, DM, Probiotics, Inflammatory Cytokines, AMPK, mTOR, ROS.

A NOVEL APPROACH IN COLORECTAL CANCER AND DIABETES MANAGEMENT: ROLE OF METFORMIN AND RAPAMYCIN.

A NOVEL APPROACH IN COLORECTAL CANCER AND DIABETES MANAGEMENT: ROLE OF METFORMIN AND RAPAMYCIN

Gerges, Alice

Abstract

Abstract The link between colorectal cancer (CRC), diabetes mellitus (DM) and inflammation is well established, and polytherapy, including rapamycin, has been commonly adopted. However, due to the relatively weak response of CRC to rapamycin, combination with other molecules including metformin has become a potentially promising approach. 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 colorectal cancer in diabetic animals, in presence or absence of probiotics. Fifty NOD/SCIDs male mice developed xenograft by inoculating HCT116 cells into the flank; they were equally divided into diabetics (induced by STZ) and non-diabetics. Metformin was given in drinking water, whereas rapamycin was administered via i.p injections. Probiotics were added to the double therapy two weeks before the sacrifice. Assessment was performed by clinical observation, gross anatomic inspection of abdominal organs, histological analysis, mast cells and ROS activities determination, as well as, by molecular analysis of pro-inflammatory cytokines (IL- 3, IL-6 and TNF), AMPK and mTOR. A decrease in the level of tumorigenesis resulted, to various extents, with the different treatment regimens. The combination of rapamycin and metformin had no significant added effect, however, when probiotics were added 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 p-mTOR. Existing evidence clearly supports the use of rapamycin and metformin especially in the presence of probiotics. There is an immunomodulatory effect of probiotics in colorectal carcinogenesis. This study confirmed some of the effects observed in several studies and clinical trials. It also described 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. However, the application of probiotics in CRC still needs further investigation aiming to clarify its exact role and decipher in more details the involved pathways. Key words: CRC, DM, Probiotics, Inflammatory Cytokines, AMPK, mTOR, ROS.
Abstract The link between colorectal cancer (CRC), diabetes mellitus (DM) and inflammation is well established, and polytherapy, including rapamycin, has been commonly adopted. However, due to the relatively weak response of CRC to rapamycin, combination with other molecules including metformin has become a potentially promising approach. 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 colorectal cancer in diabetic animals, in presence or absence of probiotics. Fifty NOD/SCIDs male mice developed xenograft by inoculating HCT116 cells into the flank; they were equally divided into diabetics (induced by STZ) and non-diabetics. Metformin was given in drinking water, whereas rapamycin was administered via i.p injections. Probiotics were added to the double therapy two weeks before the sacrifice. Assessment was performed by clinical observation, gross anatomic inspection of abdominal organs, histological analysis, mast cells and ROS activities determination, as well as, by molecular analysis of pro-inflammatory cytokines (IL- 3, IL-6 and TNF), AMPK and mTOR. A decrease in the level of tumorigenesis resulted, to various extents, with the different treatment regimens. The combination of rapamycin and metformin had no significant added effect, however, when probiotics were added 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 p-mTOR. Existing evidence clearly supports the use of rapamycin and metformin especially in the presence of probiotics. There is an immunomodulatory effect of probiotics in colorectal carcinogenesis. This study confirmed some of the effects observed in several studies and clinical trials. It also described 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. However, the application of probiotics in CRC still needs further investigation aiming to clarify its exact role and decipher in more details the involved pathways. Key words: CRC, DM, Probiotics, Inflammatory Cytokines, AMPK, mTOR, ROS.
CRC, DM, Probiotics, Inflammatory Cytokines, AMPK, mTOR, ROS.
A NOVEL APPROACH IN COLORECTAL CANCER AND DIABETES MANAGEMENT: ROLE OF METFORMIN AND RAPAMYCIN.
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/10447/337960
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