A Retrospective In Vitro Study of the Impact of Anti-diabetics and Cardioselective Pharmaceuticals on Breast Cancer

作者：Szewczyk M; Richter C; Briese V; Richter D U^*

来源：Anticancer Research, 2012, 32(5): 2133-2138.

• Beta-blockers
• anti-diabetics
• breast cancer
• propranolol
• bisoprolol
• glitazone
• metformin
• MCF7
• BT20
• cell lines

Background: In a retrospective controlled study, a tumor-protective effect, regarding breast cancer, was determined for the medicines metformin and glitazone (antidiabetics), bisoprolol, and propranolol (cardioselective beta 1 adrenoceptor antagonists). Our main goal was to provide evidence, showing the tumor-protective effects of beta-blockers and of antidiabetics via investigations in vitro. Materials and Methods: Four different medicines were tested in cell cultures: Propranolol: 2.4 mg/ml and 0.3 mg/ml; bisoprolol: 0.1 mg/ml and 0.05 mg/ml; metformin: 7.5 mg/ml, 2.5 mg/ml, and 0.15 mg/ml; and glitazone: 2.5 mg/ml, 0.15 mg/ml, and 0.05 mg/ml. The human breast cancer cell lines MCF7 and BT20 (estrogen receptor-positive and -negative; ATCC; cell density: 5x10(5) cells/ml) were used. Both cell lines were cultured under sterile conditions in incubators at 37 degrees C, with a humidified atmosphere of 5% CO2. The influences of the drugs were determined through cytotoxicity and proliferation assays and performance of a hydrogen peroxide assay. Morphological observations (light microscopy) and metabolic investigations (pH value, glucose) were also performed. Results: The application of the beta-blocker propranolol resulted in highly cytotoxic effects (%26gt;90%) in both cell lines. In contrast, bisoprolol did not have any effects, neither in cytotoxicity tests nor in cell proliferation assays. The anti-diabetic metformin had a higher cytotoxic influence on the BT20 than did on the MCF7 cell line. The cell proliferation of BT20 was significantly inhibited after the addition of 2.5 mg/ml metformin and of 2.5 mg/ml glitazone. The application of glitazone also resulted in an increase of hydrogen peroxide and a decrease of the pH value. Conclusion: The strongest cytotoxic effect was observed with propranolol suggesting that, in clinical practice, this pharmaceutical can be used in patients with breast cancer who have hypertension. A specific clinical recommendation for anti-diabetics is not yet possible.

• 出版日期2012-5