Anti-tumor Effects And Mechanisms Of Zinc Pyrithione In Gastric Cancer

Gastric cancer is the fourth largest cancer in the world,while China is a country with great high incidence of gastric cancer.Due to inadequate early screening,patients were often at advanced stages of gastric cancer when been detected.Traditional gastric cancer is mainly resected by surgery combined with radiotherapy and chemotherapy.It still has a high recurrence rate though it brings partial survival benefits.Targeted therapy and immunotherapy have brought new horizon for the treatment of gastric cancer,but both targeted nor immunological drugs were limited and cannot fit the large number of patients with gastric cancer,thus more gastric cancer drugs need to be developed or discovered.In this project,high-throughput drug screening platform was used to screen out Zinc Pyrithione a potential drug for gastric cancer from the FDA library.Cell and molecular biological methods were then used to find out the inner mechanisms that Zinc Pyrithione inhibits gastric cancer cells.Zinc Pyrithione induces anoikis-like cell death which is caused by the accumulation of ROS.After detection of apoptosis-related proteins and co-treatment of cells with caspase inhibitor,Zinc Pyrithione was found to induce apoptosis not through caspase-dependent way,but via aif-related way.In addition,Zinc Pyrithione inhibits self-protective autophagy in gastric cancer cells and was achieved by lysosomal membrane permeability.In addition to inhibiting gastric cancer cell lines in vitro,Zinc Pyrithione inhibits the tumor growth in tumor xenografts model.Our study showed that Zinc Pyrithione has the potential as a clinical drug for gastric cancer.