Investigation of the effects of a novel silver (Ag) carbene complex on colon cancer in rats

Cancer is a major global health problem with major therapeutic challenges. Colorectal cancer is among the leading causes of death worldwide. The incidence of colorectal cancer (CRC) is increasing rapidly. The incidence of CRC is predicted to double worldwide by 2035. Due to the high mortality rate of CRC and the development of effective but less toxic chemotherapeutic agents for the treatment of CRC, new treatment methods are constantly being researched. Today, it is seen that chemotherapeutic drugs obtained with silver (Ag) components are effective on cancer. In this thesis, the effects of Silver Carbene (AgC) complex, a new silver component, on colorectal cancer as a potential anticancer agent against colorectal cancer have been investigated. For this purpose, 90 Spraque dawley type rats were divided into 6 groups and used. These groups are i. Control; 0.9% sterile saline is applied once a week for 3 weeks, ii. Silver Carben I (AgC I); Silver carbene complex (1 mg / kg, 1 mL / rat) dissolved in DMSO and diluted with drinking water, administered by oral gavage every other day, iii. Silver Carben II (AgC II); Silver carbene complex (2 mg / kg, 1 mL / rat) dissolved in DMSO and diluted with drinking water, administered by oral gavage every other day, iv. Dimethyl Hydrazine (DMH); administered at 15 mg/kg body weight once a week, v. Dimethyl Hydrazine + Silver Carben I (AgC I); DMH (15 mg/kg body weight once a week) + silver carbene complex (1 mg/kg, 1 mL/rat) dissolved in DMSO and diluted with drinking water, administered by oral gavage every other day, vi. Dimethyl Hydrazine + Silver Carben II (AgC II); DMH (15 mg/kg body weight once a week) + silver carbene complex (2 mg/kg, 1 mL/rat) dissolved in DMSO and diluted with drinking water applied by oral gavage every other day. At the end of our study, which has lasted for 24 weeks in total, no crypts have been formed in the colon tissues of the Control, AgC I and AgC II groups; It has been determined that in the DMH applied group 78, in the DMH + AgCl I group; 29 and in the DMH + AgC II group; 20 crypts have been formed. It has been determined that there has been a significant decrease in the number of crypts in the colon tissues in the groups in which the Silver Carbene complex has been applied, compared to the group in which only DMH has been applied.The results obtained from the western blot study show that Bax, Caspase-3 and Caspase-9 protein expressions in the colon tissues of the silver carbene treated treatment groups statistically increased significantly compared to the DMH groups (p<0.0001), Bcl-2, Akt1, p-Akt1, PI3K, p-PI3K, mTOR, p-mTOR protein expressions show a statistically significant decrease (p<0.0001). These results show that the silver carbene complex exhibits anti-colon cancer activity through inhibition of the PI3K/AKT/mTOR signaling pathway and activation of the apoptotic pathway. Therefore, it is thought that the Silver Carbene complex may have a curative effect on colorectal cancer. Keywords: Apoptosis, Silver Carbene, Colorectal Cancer