Proliferation Inhibition And Mechanism Of Prostate Cancer Cells By Drugs Combination

Prostate cancer is malignant tumor which occurs in men with prostate tissue. The incidence rate of prostate cancer in China has rapidly increased in recent years. This disease gradually progresses from androgen dependence to late stage androgen independence. Chemotherapy is ineffective and has toxic side effects. Therefore, it is difficult to treat these patients. Among modern medical therapeutic methods, especially cancer therapeutic methods, combination therapy has become a trend. When monotherapy is adopted, curative effect can not be increased by dose increase, because side effects will also be increased. Meanwhile, a lot of anti-tumor drugs have side effects that can endanger patients" life. Combination of drugs with non-overlapping side effects can not only reduce the side effects, but also increase the synergy effects.In this paper, we chose PC-3prostate cancer cell lines as the main research subjects, studied the effects of different clinical medicine and natural medicine combination on prostate cancer cells. Three parts were included:(1) Use MTT assay and trypan blue exclusion assay to screen the effects of combinations of statin cholesterol-lowering drug atorvastatin and a series of non-steroidal anti-inflammatory drugs on inhibiting prostate cancer PC-3cell growth and analyze the possible mechanisms;(2) Screen the effects of natural product curcumin and its metal complexes and compounds containing metal ions combination on the growth of prostate cancer PC-3cell line;(3) Atorvastatin and antihypertensive drugs hydrochlorothiazide alone or in combination on growth inhibitition of prostate VCaP-N cells, PC-3cells, CWR cells, pancreatic cancer Panc-1cells and HT-29colon cancer cells were determined by trypan blue exclusion assay and luciferase reporter gene analysis.The results showed that,(1) Atorvastatin in combination with salsalate had stronger effects on growth inhibition and apoptosis of PC-3cells than either agent used individually. Treatment with atorvastatin (5μM) or salsalate (5μM) alone caused a20%and19%decrease in the number of viable cells. While a combination of atorvastatin (5μM) and salsalate (5μM) caused a43.9%decrease in viable cells compared with the control. The level of activated Akt in PC-3cells treat with atorvastatin and salsalate alone after24h is0.85and1.09respectively, while the combination of them is0.58.(2) Growth inhibition rate of curcumin metal complexes to PC-3cells is as follows:CurV, CurZnl:2and CurBi show-strong inhibition, which IC50values are0.5,5.8and5.1μM. The PC-3cells growth inhibitition rate(%of control) of single administration group were11.8%and5.7%, while combined treatment group was34.7%;(3) The CWR cells growth inhibitition rate(%of control) of single administration group were33.1%and28.1%, while combined treatment group was80.7%; The PC-3cells growth inhibitition rate(%of control) of single administration group were27.5%and17.3%, while combined treatment group was62.3%: The PC-3cells growth inhibitition rate(%of control) of single administration group were20.8%and15.1%, while combined treatment group was58.0%. The PC-3cells luciferase activity(%of control) of single administration of atorvastatin (10μM) and hydrochlorothiazide (10μM) group were89.2%and90.3%, while the combination group (atorvastatin (10μM)+hydrochlorothiazide (10μM) group) was66.5%.So we draw the conclusion that the combination group had a more potent inhibitory effect on the growth and a more potent effect on the apoptosis induction of PC-3cells than either agent alone, showing a synergistic effect. Its mechanism may be associated with the reduction of Akt protein expression. Atorvastatin combined with hydrochlorothiazide had a more potent inhibitory effect on the growth of prostate cancer cells, pancreatic cancer cells, and colon cancer cells. Since atorvastatin, salsalate and hydrochlorothiazide are already so widely used drugs in clinicals, our subject will provide a scientific basis and key reference data for prostate cancer cells inhibition and some related clinical research.