Effects of TGF-β 1 on proliferation of cancer stem cells and non-cancer stem cells of lung cancer

Objective:To study the effects of TGF-β1 on the growth of cancer stem cells and non-lung cancer stem cells of lung cancer,so as to lay a foundation for studying the molecular regulatory mechanism for proliferation and differentiation of lung cancer stem cells.Methods:Cancer cells were isolated and cultured from human large cell lung cancer specimens using a serum-free medium to establish large cell lung cancer cell line.Biologic characters of lung cancer stem cells were studied by cell sphere formation test and X-ray radiotherapy sensitive assay.The effects of TGF-β1 on the growth of cancer stem cells and non-cancer stem cells of lung cancer were analyzed by flow cytometry and cell growth inhibition test.Results:A large cell lung cancer cell line was established by primary culturing lung cancer tissues.TGF-β1 could inhibit lung cancer cell proliferation and induce them to the shape of mesenchymal cells.When CD44 and CD90 antibodies were co-stained and analyzed by flow cytometry,the lung cancer cells could be divided into 4 populations,i.e.CD44+CD90+,CD44+CD90-,CD44++CD90+ and CD44++CD90-cells.CD44++CD90+cells had the smallest population in the cell line,accounting for 0.4%;they had the strongest cell sphere formation ability and the strongest resistant ability to X-ray radiation among all the 4 populations.TGF-β1 had the weakest suppression effect against CD44++CD90+ cells and the strongest suppression effect against CD44+CD90+ cells.TGF-β1 could gradually increase the ratio of CD44++CD90+ cells when added to the culture medium.After depletion of TGF-β1 from the medium,the ratio of CD44++CD90+ cells gradually decreased again.Conclusion:CD44++CD90+ cells may be the stem cells of large cell lung cancer,and TGF-β1 can enrich lung cancer stem cells in vitro by inhibiting the non-stem cells of lung cancer.