Statins Inhibit Colorectal Carcinoma Proliferation By Down-regulating Bromodomain PHD-finger Transcription Factor

Background:Bromodomain PHD-finger transcription factor(BPTF)is the largest subunit of chromosome remodeling factor.It is involved in regulating the process of chromatin remodeling,affecting cell proliferation and differentiation,and affecting embryonic development and maturity effect.In recent years,research has found that BPTF has the effect of promoting cancer progression.BPTF is highly expressed in tumor tissues and is positively related to tumor differentiation and stage.The mechanism of action is still unclear.Blocking or inhibiting BPTF expression may inhibit tumor progression.A large number of studies have shown that statins can inhibit the proliferation of colorectal cancer cells and improve the clinical prognosis of colorectal cancer patients.This is in contrast to the role of BPTF factors in colorectal cancer.At present,there are few reports on the interaction of statins and BPTF in colorectal cancer.Therefore,by exploring the role of statins and BPTF in colorectal cancer,we hope to find new ideas and theoretical basis for treating colorectal cancer.Objective:To clarify the promoting effect of BPTF in colorectal cancer;to determine the inhibitory effect of statins on colorectal cancer cells;to explore whether the effect of statins on inhibiting the proliferation of colorectal cancer cells is played by BPTF.Methods:(1)Clinical colorectal cancer specimens were collected and compared to detect the expression of BPTF.(2)Interfering with the expression of BPTF in colorectal cancer cells,and observing the effect on the proliferation of colorectal cancer cells.(3)Two colorectal cancer cells were treated with two statins of different concentrations,respectively,to detect cell viability and migration,and to detect the expression of BPTF in each group of cells.(4)Colorectal cancer HCT-116 cells were used to perform nude mice tumor-bearing experiments in the right lower abdomen of nude mice to observe the tumor growth.The nude mice were sacrificed after 21 days of simvastatin treatment.The tumors were measured,weighed,and paraffin sections Detection of BPTF expression.Results:(1)After knocking down BPTF in two colorectal cancer cells,compared with normal colorectal cancer cells,the cell proliferation ability of the knockdown group was reduced(~*p<0.05).(2)In collected clinical specimens of colorectal cancer,immunofluorescence and immunohistochemistry indicated that the expression of BPTF was increased in colorectal cancer tissues compared with adjacent tissues.(3)After testing colorectal cancer cells for 48 hours with two different concentrations of statins,the proliferation,survival,and migration of colorectal cancer cells were measured.It was found that statins can inhibit the proliferation,survival,and migration,and the inhibitory effect was more obvious as the drug concentration gradient increased(~*p<0.05).(4)Two different concentrations of statins were used to treat colorectal cancer cells and detect the expression of BPTF.The results showed that BPTF expression in the drug group was down-regulated and was negatively correlated with drug concentration.(5)In nude mice tumor-bearing experiments,compared with the control group,the expression of BPTF in the tumor tissue of the drug-treated group decreased,and the tumor growth rate slowed down and the tumor mass became smaller(~*p<0.05).Conclusion:In colorectal cancer tissues,BPTF is highly expressed and promotes the proliferation of colorectal cancer cells;statins down-regulate the expression of BPTF and inhibit the colorectal cancer cell proliferation.