METFORMIN ANTIMETABOLIÑ THERAPY
Purpose: antimetabolic therapy is considered to be an actual direction in therapy of cancerpatients, in particular the use of biguanide metformin. However, there is not enough knowledge thatwould give us a clear understanding of the mechanisms of anticancer action. Our hypothesis was thatmetformin affects the activity of the key enzyme adenosine catabolism - adenosine deaminase, andon the level of substrate and products. We have found that metformin significantly increases theactivity of adenosine deaminase, concentration of inosine and hypoxanthine. We determined a markedincrease in the concentration of hypoxanthine which requires further study and xanthine oxidase andenzymes metabolism of methionine. Materials and methods: biopsy material of malignant tissues in 30 patients with breast cancer were divided into two groups. The first group received 1000 mg of metformin a day as well as standard preoperative chemotherapy. Results: it was determined that the concentration of adenosine in malignant tissue of patients with RMZH taking metformin was 0,226±0,148 mcmole/g of tissue, those not taking metformin had 0,186±0,056 mcmole/g of tissue. The level of inosine is 0,121±0,041 mcmole/g of tissue. It is considerably higher than the same factor in the screening group which makes up 0,042±0,015 mcmole/g of tissue (ð=0,25). Hypoxanthine showed the maximum concentration rise at metformin therapy. Its concentration in patients taking metformin made up 2,45±0,428 mcmole/g of tissue, whereas in the screening group it was just 0,711±0,269 mcmole/g of tissue (ð=0,0003). Conclusions: we determined that at metformin therapy the statistically significant increase of adenosine deaminase activity and concentration of inosine and hypoxanthine are observed. The marked increase of hypoxanthine concentration revealed by us requires further investigation of xanthine oxidase and enzymes metabolism of methionine.