The Study Of Effects Of MCLR On SMMC-7721Cells

Background:Microcystin (MC) is one of the strong toxic algal toxins which distributed widely around the world, which was considered to target liver in the past. With the further research of MC carried out, the toxic effects of MC to other organs are continued to be revealed,such as the toxicity to kidney, reproductive system, neuron andso on. At the same time, MC is also considered as a potent tumor initiator. Binding with PP2A and then inducing the inhibition of PP2A activity is considered as one of the most important mechanisms of MC’s toxicity. Furthermore, PP2A not only plays important role in normal cells, but also has important implications in the process of tumor cells’proliferation, growth and migration. Now, there are many tumor drugs are developed based on inducing the inhibition of PP2A and thereby inhibiting the growth and proliferation of tumors. Therefore we are very interested in the research about the effects of MC-LR on the tumor cells,then,we chose the SMMC-7721cells to research the effects of MCLR on it.Methods:The liver cancer cell SMMC-7721cells was selectedto study the MC-LR’s effects on the cell cycle,apoptosis,cytoskeleton and the cytoskeleton associated proteins expression and modification by using flow cytometry immunoblotting,immunofluorescence and immunoprecipitation.Results:MC-LR could enter into the cells and then inhibited the activity of PP2A,induced the phosphorylation of PP2A-C subunit and the expression of a4, increasing the binding between a4and PP2A.The treatment of MC-LR did not change the SMMC-7721cells’ cell cycle and apoptosis, but under the same treatment, there are significant changes in the cytoskeletons of SMMC-7721cells,including actin and tubulin;Furthermore, MC-LR induced the changes of some cytoskeleton associate proteins, including the phosphorylation of HSP27,VASP, cofilin and the activation of Rac1.Conclusion:MC-LR could enter into the SMMC-7721cells and combine with PP2A, it inhibited the activity of PP2A by the way of inducing the phosphorylation of PP2A-C subunit, the expression of a4and the binding between a4and PP2A;MC-LR did not induce the change of cell cycle and apoptosis, but changed the cytoskeleton of the cells;the changes of the cytoskeleton-associate proteins regulated by PP2A contribute to the changes of cytoskeleton.Significance and prospective:Our study not only has its important meaning in discovering the mechanisms of MC-LR’s effects on cancer cells,but also provide the reference for the future works:Whether MC-LR could affect the cancer cells’ adhesion, migration and others through leading to the changes of cytoskeleton, and the possibility of developing MC-LR to be an anti-cancer drug.