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Effects of TGF-β 1 on proliferation of cancer stem cells and non-cancer stem cells of lung cancer
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Abstract:
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.
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Project Supported:
Project supported by the Key Science and Technology Foundation of Henan Province (No. 0623033100), and the Key Science Foundation of Health Bureau of Henan Province( No. 200802015)
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