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Dryad

Assessing the anticancer effects of Metformin

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Jan 10, 2022 version files 52.94 KB

Abstract

Metformin is an anti-hyperglycemic biguanide drug that is widely used as the first-line prescription for managing type 2 Diabetes Mellitus (T2DM). Research suggests metformin use helps control T2DM which is one of the many risk factors for cancer and is proposed to have multiple antagonistic actions against cancer cells. Suggested biological means that metformin utilizes include AMPK-driven cascades involving two pathways, a direct and an indirect one. This leads to a decrease in the mechanistic activity of rapamycin (mTOR), folate level, c-MYC, NF-B, and also increases P53 phosphorylation. These cascades will also decrease cyclin D1, reactive oxygen species (ROS), and increase mTOR Complex1 (mTORC1) concentrations, apoptosis, and autophagy. Some researchers suggest metformin also exerts anti-inflammatory effects through reducing Interleukins-6 (IL6) and 8 (IL8), inhibition of protein translation via LKB1, increasing expression of GPD1 which suppresses cancer by inhibiting mitochondria and inducing cell apoptosis, and inhibiting leptin while increasing adiponectin production. There is also evidence of possible suppressive effects on overexpressed signals in some cancers, such as Notch1/Hes1, STAT3, and HER2+ which ultimately could increase survival rates in cancer patients.

Our goal is to explore the mechanisms in which metformin can act as an anticancer drug and assess the effect of metformin on various types of malignancies.

We retrospectively studied 266 cancer patients diagnosed in 2018 – 2019 in King Fahd Hospital of the University (KFHU). This population was furtherly divided into non-diabetic and diabetic cancer patients and the latter group into those who received metformin and those who did not.

The results showed the statistical significance of metformin use on the cancer grade at diagnosis that favourably influences the morbidity/mortality.

Metformin might have an anti-cancer effect on the grade of cancer at the time of diagnosis regardless of its dosage, and this might improve the prognosis of malignancy.