The anti-tumor activity of andrographolide on breast cancer of mice and its mechanism / 中国药理学通报

ABSTRACT

Aim To evaluate the effects of androgra- pholide ( Andro) on suppressing tumor growth and improving mitochondrial function on mouse breast cancer and explore its mechanism.Methods MTT assay was performed to measure the effect of Andro on the growth capacity of mouse breast cancer cell line 4T1.Mice were treated with Andro, then tumor volume measured, organ index calculated and Hematoxylin - eosin ( HE ) stained to detect the inhibitory effect of Andro on tumors.Lactate assay kit was used to detect the lactate level in mouse serum to check glycolysis discrepancy.To illustrate the transformation in oxidative phosphorylation ( OXPHOS) , Acetyl coenzyme A ( Acetyl-CoA ) assay kit was used to ascertain Acetyl-CoA content level , Western blot was used to detect the protein expression of pyruvate dehydrogenase ( PDH) , and ATP assay kit was used to ascertain ATP content level.The mitochondria functions were analyzed oxygen ( ()2 ) consumption was measured by Clark oxygen electrode, and mitochondrial membrane potential was detected by JC-1 staining.Results Andro could effectively inhibit the proliferation of 4T1 cells and the growth of tumors, and had no significant damage on normal organs.An- clro reduced serum lactic acid content, indicateing that Andro inhibited the process of glycolysis.The expression of PDH, content of acetyl-CoA and ATP content increased with the increase of Andro concentration.It showed that Andro could up-regulate oxidative phosphorylation.In addition, the ()2 consumption and mitochondrial membrane potential increased in 4T1 cells, indicating that Andro could recover mitochondrial function.Conclusions Andro can inhibit the growth of mouse breast cancer, and its mechanism may be related to the inhibition of glycolysis level, restoration of OXPHOS and improvement of mitochondrial function.