| dc.description.abstract | Colorectal cancer is the third most common cancer in men and the fourth most common cancer in Iranian women, and recurrence and metastasis are the main causes of death in patients with this cancer. Cancer stem cells have been proposed as the main factor involved in metastasis and cancer invasion. The purpose of this study is to investigate the mechanism of melatonin effect, fundamental characteristics and drug resistance in oxaloplatin resistant cells of colon cancer cell lines.
Literature review: The initial studies on the possible connection and effects of melatonin with cancer began in 1960. However, the most attention in this field was in 1978 when Cohen and his colleagues expressed the theory of the possible role of the pineal gland in the etiology of breast cancer, which reduced the function of the gland. Pineal and melatonin secretion induce hyperestrogenism and mammary tumors. Studies have shown that many cancers such as breast, lung, brain, and hepatocellular carcinoma are sensitive to melatonin treatment. Melatonin has its oncostatic effects through antiproliferative, antimetastatic, apoptosis induction, anti It acts as an oxidant, anti-angiogenesis, anti-inflammatory and modulating and reducing the expression of oncogenes.
Main methods: First, resistance of LS174T colon cancer cell line to oxaloplatin drug was increased by using IC50 concentrations that included resting periods. Cytotoxicity and induced apoptosis were evaluated by MTT and flow cytometry techniques, respectively. ABCB1, Bax, Bcl-2, MT1 and MT2 gene expression levels were also investigated using qRT-PCR technique under stress and non-stress conditions. P-gp activity was evaluated by fluorometric technique.
Key finding: The value of IC50 in sensitive LS174T cells increased from 500.7 nM to 7119 nM in resistant cells. The expression levels of Bax, MT1 and MT2 genes in chemotherapy-resistant cells have decreased compared to sensitive cells, while a significant increase in Bcl-2 mRNA and ABCB1 mRNA expression was observed (P < 0.001). Toxicity assays, MTT, and flow cytometry, showed that the combined use of oxaloplatin and melatonin has synergistic effects on oxaloplatin-induced cytotoxicity. | en_US |
