The Research Of Taraxasterol,Propofol And Remimazolam On Inhibiting Proliferation And Tumor Growth Of Prostate Cancer Cells

Prostate cancer is the most common malignancy in men,ranking second in morbidity and fifth in mortality among male tumors.The pathogenesis of prostate cancer is very complex.Multiple physiological processes,genes and signaling pathways are involved in the development and progression of prostate cancer.Androgen deprivation therapy by surgical or chemical castration is currently the most commonly used and effective treatment for prostate cancer patients.However,prostate cancer patients often develop drug resistance,metastases and die.With complex pathogenesis and sharply declining survival rate,it is urgent to find new effective antitumor drugs to maintain the life of prostate cancer patients.The purpose of this study is to find new drugs that inhibit the proliferation of prostate cancer cells and tumor growth,and to explore the function and effect of new natural drugs and existing clinical drugs in anti-prostate tumor.Taraxasterol is a kind of pentacyclic triterpenoids with various biological activities,which can be extracted from many types of plants.It has anti-inflammatory and antioxidant properties and can inhibit the growth of tumor cells in a variety of cancers.However,the effect and mechanism of taraxasterol on the growth of prostate cancer cells in vitro and in vivo have not been revealed.In this study,taraxasterol significantly inhibited the proliferation of prostate cancer cells and the growth of xenografts in nude mice,and down-regulated the expressions of proliferation-related proteins c-Myc and cyclin D1.The mechanism was further explored and confirmed that taraxasterol inhibited the activation of PI3K/AKT signaling pathway and decreased FGFR2 expression in prostate cancer cells.These results suggest that taraxasterol can inhibit the proliferation of prostate cancer cells and tumor growth by affecting FGFR2-PI3K/AKT signaling axis,which provides a theoretical basis for its application as a potential drug in the clinical treatment of prostate cancer.Propofol is one of the most widely used intravenous general anesthetics in clinical practice.In addition to its anesthetic effect,propofol plays a cancer suppressive role in various types of cancer and improves the overall postoperative survival of patients with various types of cancer.Studies have shown that propofol can inhibit the transcription activity of androgen receptor and the expression of hypoxia-inducing factor HIF-1α in prostate cancer cells,but the key target gene of propofol regulating the proliferation of prostate cancer cells has not been found yet.Remimazolam is a new ultra-short-acting anesthetic with good sedative effect,which can be used for sedation and general anesthesia.At present,there are few in vivo studies related to remimazolam,and whether remimazolam has an effect on prostate cancer cells has not been reported.This study found that propofol and remimazolam independently or synergically inhibited the proliferation and the colony formation ability of prostate cancer cells,and down-regulated the expressions of proliferation-related proteins c-Myc and cyclin D1.The common targets of propofol,remimazolam and prostate cancer were analyzed by network pharmacology,and found STAT3,which is most closely related to the HIF-1α pathway.Western blotting and Real-time q PCR experiments verified that propofol and remimazolam can inhibit the expression of STAT3 in prostate cancer cells alone or synergistically,which indicates that propofol and remimazolam exert the function of inhibiting the proliferation of prostate cancer cells through the STAT3 target in the HIF-1α pathway.The selection of anesthetic drugs and methods that inhibit the proliferation of prostate cancer cells and tumor growth during surgery may reduce the risk of cancer recurrence and is a better treatment for prostate cancer.