转化生长因子β1正反义基因对人肺巨细胞癌细胞体内外增殖的影响

探讨人转化生长因子β１（ＴＧＦβ１）正反义基因对人肺巨细胞癌细胞（ＰＬＡ－８０１Ｄ）增殖的影响及调控。方法通过基因转染方法,将ＴＧＦβ１正、反义基因分别导入ＰＬＡ－８０１Ｄ细胞,观察转染和未转染细胞体内外增殖变化、ｎｍ２３基因和ｃ－ｍｙｃ基因表达以及细胞凋亡特征。结果与未转染细胞比较,正义ＴＧＦβ１基因转染细胞培养上清中ＴＧＦβ１活性增加,体外生长速度减慢,软琼脂细胞培养集落形成能力降低,裸鼠体内成瘤率下降约４７％,肿瘤的转移受到抑制。其机制可能与正义ＴＧＦβ１基因转染细胞ｎｍ２３基因表达增加,ｃ－ｍｙｃ基因表达减少以及诱发细胞凋亡有关。而反义ＴＧＦβ１基因转染细胞则出现相反结果。结论ＴＧＦβ１对ＰＬＡ－８０１Ｄ细胞的体内外生长具有负调控作用

Influence of transfection of sense- and antisense-TGF beta 1 gene on human pulmonary giant cell carcinoma cell proliferation

OBJECTIVE: To investigate the effect of human sense- and antisense-transforming growth factor beta 1 (TGF beta 1) gene on human pulmonary giant cell carcinoma cell (PLA-801D) proliferation. METHODS: PLA-801D cells were transfected with an expression vector containing a full length human sense- or antisense-TGF beta 1 gene by gene transfer. The changes of cell proliferation, expressions of nm23 mRNA and c-myc mRNA and the feature of apoptosis were studied on transfected cells and untransfected cells. RESULTS: The cells transfected by sense-TGF beta 1 gene showed higher TGF beta 1 activity in the conditioned media, growth inhibition in vitro and decreased coloning formation in anchorage-independent assay. The tumorigenic rate was reduced about 47%, the metastasis was inhibited in athymic nude mice as compared with untransfected cells group. The mechanism of such changes described may be associated with the higher expression of nm23 mRNA, and the lower expression of c-myc mRNA as well as the apoptosis in sense-TGF beta 1 gene transfected cells. However, opposing changes were observed in the antisense-TGF beta 1 gene transfected cells. CONCLUSION: TGF beta 1 acts as a negative growth regulator of the PLA-801D in vitro as well as in vivo.