The Rna Binding Protein Tristetraprolin Inhibits Cell Proliferation Of Lung Adenocarcinoma Cells In Vitro

Objective:To investigate the effects of tristetraprolin(TTP)on lung cancer cell proliferation and to explore the relative mechanism.Methods: The human lung adenocarcinoma cells with tetracyclineinducible expression regulatory system were established.Western blotting and QPCR were used to confirm the over-expression of TTP after the doxycycline(Dox)treatment.Effect of TTP on the proliferation,migration and the colony forming capacity were estimated by cck-8,transwell and colony forming unit test respectively.The cell apoptosis and cell cycle were measured by flow cytometry.The protein expressions of cellular apoptosis-related and autophagy-related genes were determined by Western blotting.The autophagic vacuoles number was assessed by transmission electron microscopy.Results: The regulated expression of TTP was established in lung adenocarcinoma cells after adding Dox.The cell proliferation,migration(H1975 :P<0.01,H1299: P<0.001)and colony forming capacity were inhibited(all P<0.0001)after TTP overexpression in lung adenocarcinoma cells H1975 and H1299.The cell cycle was arrest at S stage of H1975(P < 0.01),but TTP overexpression didn’t elicited cellular apoptosis.The protein levels of autophagy-related genes including Beclin1(H1975 : P<0.001,H1299: P<0.01)and LC3 II /LC3Ⅰ(H1975:P<0.01,H1299: P<0.001)decreased in the TTP overexpression groupcompared with control group in the lung adenocarcinoma cancer cells.Transmission electron microscopy revealed the decline of the autophagic vacuoles number after TTP over-expression.Conclusion: Cell proliferation,migration and colony forming capacity of the lung adenocarcinoma cells were obviously inhibited by TTP overexpression,and cell cycle was arrested at S stage,which is probably through regulation of autophagy not apoptosis.