Study On The Mechanism Of Induction Of Apoptosis And Autophagy By Natural Small Molecule,STE011,in Human Pancreatic Cancer Cells

Objective:It has been reported that selaginella tamariscina possesses effect on variety of cancers.However,the active site and the active components are still not clear.In this study we aimed to explore the anticancer effect of STE011,a compound extracted from selaginella tamariscina,on human pancreatic cancer cells in vitro and elucidate the underlying mechanisms.Methods:(1)Cell viability was detected by MTT assay.(2)The biological functions of STE011 were investigated by wound-healing assays in AsPC-1 cells.(3)The morphological changes of apoptosis or autophagy were observed by light microscopy and electron microscopy.(4)Cell apoptosis were tested by flow cytometer staining with Annexin V/Propidium iodide(AV/PI).(5)Western blot was used to detect the expression leve of associated functional proteins.Results:(1)STE011 inhibited cell viability in pancreatic cancer cells(AsPC-1 cell and PANC-1 cell)(P<0.05)in a time dose dependent manner.Then STE011 inhibited HPDE6-C7 smaller(P<0.05).STE011 had inhibitory effect on pancreatic cancer cells proliferation.(2)Compared with the control group,STE011 significantly shortened the distance between AsPC-1 cell migration.(3)Compared with the control group,The percent of apoptosis cells and the ratio of Bax/Bcl-2 of AsPC-1 were obviously increased in STE011 group,and lowed the expression of caspase-3 and caspase-9,showing that STE011 induced AsPC-1 cell apoptosis.(4)Compared with the control group,the autophagosome produced in AsPC-1 cell could be observed by Electric Transmission Microscope,and more expression of LC3-Ⅰ was turned into LC3-Ⅱ,confirming that STE011 induced AsPC-1 cell autophagy.(5)Compared with the control group,the expression of Akt,p-Akt and p-p65 significant was decreased in STE011 group,demonstrating STE011 induced AsPC-lcell apoptosis and autophagy through targeting Akt/NF-κB signaling pathway.Conclusions:Our study found that STE011 showed significantly the inhibition of cell proliferation and migration,and the induction on apoptosis and autophagy of AsPC-1 cells as result from the stimulation of ROS generation,and the action may be through targeting on Akt/NF-κB signaling pathway.The present work provides pharmacological evidence that STE011 exhibits potential use and possibly will be developed a new drug in the treatment of pancreatic cancer.