Regression Of Castration Resistant Prostate Cancer By A Novel Compound HG122

Prostate cancer (PCa) is an aggressive disease which occurs most often in world. On the basis of statistics of world and the U.S.A at 2015, PCas morbidity ranks top two and mortality remain less than sixth because of a higher level life. Recent years, Chinese PCas sufferers have continued to accumulate and the overall upward trend is rising which means it will soon reach western levels.Prostate cancer is a kind of hormone sensitive solid tumor that is very sensitive to androgen deprivation therapy (ADT). Clinical and chemical castration are the mainly treatments in the early phase, while the big advantage is they could stop androgen synthetize at the source, then androgen receptor (AR) pathway is blocked and PCa cells cannot survive. But after average 18-24 mouths, PCa progress to a more malignant castration resistant prostate cancer (CRPC) in most cases. Androgen receptor signaling pathway has proven pivotal at the process of growth and expansion in both prostate and PCa tissue. As soon as androgen bining to its receptor, androgen response elements (AREs) are activated, a series of co-activator proteins are attracted and other cellular signaling pathways start to make cells grow and proliferate. AR has been considered as a crucial factor to CRPC, and the study of AR as potential therapeutic target in CRPC may be helpful in disease control and life cycle management.In this study, we obtained a potent small molecule compound HG122 through screening its inhibitory effects on AR signaling pathway from the compound libraries of our laboratory. HG122 suppressed CRPC cells growing and metastasis, and inhibited tumor growth both in subcutaneous tumor model and in situ model. In addition, we noticed that HG122 reduce the expressed PSA and TMPRSS2 downstreaming AR pathway without violating AR. And HG122 promoted AR protein degradation through proteasome path. This may be the potential mechanism of HG122 against CRPC through AR signaling pathway. In a word, these results had certain reference value to the further research.