| BackgroundRenal cell carcinoma(RCC),referred to as kidney cancer,is a malignant tumor that originates from renal tubular epithelial cells and accounts for the third most common malignant tumor in the urinary system,of which 75%are clear cell renal cell carcinoma(ccRCC).In the past few decades,although the death rate of renal cell carcinoma has been declining,its incidence has continued to increase.Surgical resection is the main method of early renal cancer,but 25%of patients have progressed or metastasized at the time of treatment.In addition,kidney cancer is not sensitive to chemotherapy and radiotherapy.Current targeted,endocrine,and immunotherapy are relatively ineffective and have a poor prognosis.In clinical practice,Chinese herbal medicine has been widely used in anti-tumor therapy,and the extracted compounds are also used to screen new anti-tumor drugs.Esculetin(Esc)is one of the coumarins in the natural Chinese herbal medicine Qinpi,Research has found that Esculetin has anti-inflammatory,anti-cough and asthmatic,anti-bacterial effects.In addition,studies have shown that esculetin has anti-tumor effects,such as in leukemia,colon cancer,pancreatic cancer and so on.However,the effect of esculetin on clear cell renal cell carcinoma has not yet been studied.Therefore,this experiment intends to preliminarily explore the effects of esculetin on the proliferation,cycle and apoptosis of renal clear cell carcinoma,and provide an experimental basis for further observation of esculetin on the biological behavior of clear cell renal cell carcinoma as well as for further exploration of Chinese herbal medicine.The potential clinical application of the treatment of kidney cancer lays a solid theoretical basis.ObjectivePreliminary study of the effect of esculetin on the proliferation,cycle and apoptosis of clear cell renal cell carcinoma,to provide a preliminary basis and ideas for further elucidating its mechanism.MethodIn this experiment,clear cell renal cell carcinoma 786-0 and SN12-PM6 cells were selected and given different concentration gradients of corticoline(0,12.5,25,50,100,200,400,800?g/ml),of which 0?g/ml was In the blank group,12.5,25,50,100,200,400,800?g/ml were the treatment groups.After 24h or 48h culture,the effect of esculetin on clear cell renal cell carcinoma 786-O and SN12 was detected by MTS method and plate clone formation experiment.The effect of esculetin on the cell cycle and apoptosis of clear cell renal cell carcinoma 786-O and SN12-PM6 was detected by flow cytometry,and the expression of cycle and apoptosis-related proteins were detected by Western Blot experiment.ResultsEsculetin can inhibit the proliferation of clear cell renal cell carcinoma 786-O and SN12-PM6 cells(P<0.05),and it is concentration and time dependent.Compared with the blank group(0?g/ml),esculetin treatment group(100,200?g/ml)S phase ratio was significantly reduced,G0/G1 phase and G2/M phase ratio was significantly increased,and the apoptotic rate was also significantly increased(P<0.05,P<0.01).Compared with the blank group(0 ?g/ml),The expressions of Cyclin D1,CDK4,CDK6,and c-Myc in the treatment group of esculetin(100,200 ?g/ml)were significantly reduced,but there was no significant difference in the expression of Caspase 3,and the expression of Cleaved Caspase 3 was significantly increased(P<0.05,P<0.01).ConclusionEsculetin can effectively inhibit the proliferation of clear cell renal cell carcinoma 786-O and SN12-PM6 cells,and induce cell cycle by down-regulating the expression of Cyclin D1,CDK4,CDK6,and c-Myc,and up-regulating the expression of Cleaved Caspase 3 Apoptosis.Esculetin can significantly affect the proliferation,cycle and apoptosis of renal clear cell carcinoma,and it is a potential new therapeutic drug for the treatment of clear cell renal cell carcinoma... |
PDF Full Text Request