The Effect Of Baicalein On Pancreatic Cancer And Its Mechanism

Baicalein,also as 5,6,7-Trihydroxyflavone,a flavone ingredient of Scutellaria baicalensis Georgi,is a promising anti-cancer agent and one of the most effective active ingredients of Scutellaria baicalensis Georgi,it has a wide range of pharmacological activity.Baicalein has low toxicity.In recent years,many domestic and foreign researches and reports have confirmed that it has potential anticancer and antitumor activities.It can induce tumor cells apoptosis,anti angiogenesis and tumor cells differentiation.It has been proved that Baicalein can inhibit the growth of pancreatic cancer cells and promote the apoptosis.However,its potential antipancreatic cancer effects and the underlying mechanisms are still unclear.In this study,we firstly proved that the viability of cancer cells gradually decline with the increase of Baicalein concentrations and processing time by CCK-8.To explore the mechanism of how Baicalein inhibits the cell growth,we proved that Baicalein could inhibit the cell proliferation by immunostaining and making the stagnation of the cell cycle at G0 / G1 phase with Flow cytometry cycle detection.The results of AnnexinV FITC-PI indicated that the number of cells apoptosis of early and late stages was increased and the apoptosis protein levels were upregulated.Most of the previous studies have shown that Baicalein can promote the apoptosis and autophagy of pancreatic cancer cells to a certain extent,but there were few studies on proliferation and movement.Notably,Baicalein exhibited little toxicity to the normal human liver HL-7702 and Kidney cells 293 T,however,the specific mechanism remains to be further explored.We further discovered that Baicalein suppressed BxPC-3 and PANC-1 proliferation and invasion through targeting NEDD9,a Cas scaffolding protein,decreasing Akt and ERK activities.To further demonstrate the role of NEDD9 in the treatment of pancreatic cancer cells with Baicalein,we transfected siNEDD9 into pancreatic cancer cells to reduce its expression.Then we found that the growth and molitily of cancer cells were inhibited,which was consistent with the treatment of Baicalein.Especially,Baicalein decreased Akt phosphorylation at T-308 via lowering NEDD9-dependent PDK1 expression.Overexpression of NEDD9 effectively rescued proliferation and invasion of BxPC-3 and PANC-1 cells treated with Baicalein.However,overexpression of NEDD9 almost had no effect on apoptosis of BxPC-3 and PANC-1 cells.In our views,we think that the mainly regulatory pathways of NEDD9 in pancreatic cancer were involved in proliferation and invasion.Taken together,our findings suggest that Baicalein is a potent remedy that could be applied to pancreatic cancer treatment in the future.