The Autophagy Induced By Baicalein In Prostate Cancer

Prostate cancer(PCa) as a most common malignant cancer seen in western men, has always been a serious threat for the health of aging males. In clinical,androgen deprivation endocrine therapy has been the most useful therapy for the early stage of prostate cancer. But the fail in the treatment of hormone refractory prostate cancer(HRPC) leads to the search of new drugs, as well as new therapy.And proteasome inhibitor as a novel anticancer drug, including NPI-0052, has widely raised the attention of scientists all over the world. Clinical studies has confirmed that proteasome inhibitor not only act as tumor suppressor, but also work as an potential autophagy inducer in some time. And the autophagy inducer property has been discovered in many cancers. For many cases, it is an antagonist for anticancer activity of proteasome inhibitor, which is the main cause of drug tolerance in cancer cells.For baicalein, a new proteasome inhibitor, can induce apotosis, cell cycle arrestment and other proliferation inhibition in PCa cells in vitro. The early study found that baicalein can dramatically induce cell apotosis and proliferation inhibition in prostate cancer, whereas the curative effect is not so evident in prostate cancer transplanted nude mice. And further research discovered that baicalein can also induce autophagy in PCa cells, exhibiting the increase of autophagosome and enhancement in the aggregation of autophagosome. But the relationship between autophagy and anticancer activity of baicalein and the autophagy induction mechanism has not been discovered.And the latest study finds that the PI3K/AKT/m TOR signaling pathway, acting as important signaling pathway in prostate cancer, is involved in the growth,proliferation and angiogenesis process. And PI3K/AKT/m TOR signaling pathway,together with the downstream NF-κB and GSK-3β signaling pathway, also plays an important role in the bioactivity induced by baicalein. And recent studies has confirmed that PI3K/AKT/m TOR signaling pathway and the downstream NF-κB and GSK-3β signaling pathway involve in the formation of autophagy in many cancers, whereas the autophagy induction mechanism in prostate cancer has not been figure out. And the relationship between autophagy and the former pathways is still need more study. Hence, to figure out the relationship between autophagy and apotosis, the research analyzed the activity of the two pathways by the combined treatment of autophagy inhibitor and apotosis inhibitor and further clarify the effect of apotosis and autophagy in cell death induced by baicalein. In addition, the project assessed the change of cytological level of the treated prostate cancer, mainlyincluding the change of autophagy level, downstream pathway of NF-κB, GSK-3βand PI3K/AKT/m TOR signaling pathway. In fact, baicalein can really work on the PI3K/AKT/m TOR signaling pathway, led to the inhibition of PI3K/AKT/m TOR signaling pathway and the downstream pathway of NF-κB, GSK-3β, and further raise the autophagy level. And this indicates that PI3K/AKT/m TOR signaling pathway is important for autophagy formation. Meanwhile, the former results not only give us reliable explanation for the drug resistance in baicalein treated prostate solic tumor cells, but also offer us a useful reference for the research of baicalein in other cancers.