转化生长因子α及孕激素对子宫内膜癌细胞增殖、侵袭能力的影响

目的观察转化生长因子α（TGFα）及孕激素对子宫内膜癌细胞增殖及侵袭、转移能力的影响,探讨TGFα及孕激素对子宫内膜癌孕激素耐药发生的影响及机制。方法研究对象为子宫内膜癌Ishikawa细胞,经不同浓度TGFα及醋酸甲羟孕酮（MPA,1μM）处理,后分别采用MTT法、划痕实验及蛋白印迹法（Western-blot）,检测TGFα、MPA,观察TGFα、MPA及二者联合对子宫内膜癌Ishikawa细胞增殖、迁移运动能力的影响,及对细胞周期蛋白D1（CyclinD1）、E-钙粘附蛋白（E-cadherin）表达的影响;DMSO溶剂对Ishikawa细胞增殖、迁移运动能力的影响作为对照。结果 MTT法检测结果示,与对照组比较,TGFα促进Ishikawa细胞的增殖（P〈0.05）,MPA抑制Ishikawa细胞的增殖（P〈0.05）,TGFα降低MPA对Ishikawa细胞的抑制作用;划痕实验结果示,TGFα组及MPA、TGFα联合组划痕处基本铺满细胞,对照组及MPA组均未铺满细胞。Western-blot法结果示,在TGFα作用下,Ishikawa细胞CyclinD1的表达升高,E-cadherin蛋白的表达降低;MPA与TGFα的作用相反,TGFα联合MPA与TGFα单独作用的结果相一致。结论 TGFα促进子宫内膜癌Ishikawa细胞的增殖及迁移运动能力,拮抗MPA的抑制作用,其机制可能通过上调CyclinD1的表达及下调E-cadherin的表达而发挥作用。TGFα分泌的增加促进子宫内膜癌孕激素治疗失败的发生。

Effect of transforming growth factor alpha and progestin on the proliferation and invasiveness of endometrial carcinoma cells in vitro

Objective To observe the effect of transforming growth factor alpha（ TGF伪） and progestin on the proliferation and the capacity of invasion and metastasis of endometrial carcinoma cells and explore their impact on progestin-resistant occurrence in the treatment of endometrial carcinoma and its potential mechanism. Methods The cultured in vitro Ishikawa cells of endometrial carcinoma were served as research object. After treatment with TGF伪（ different concentration） and medroxyprogesterone acetate（ MPA,1渭M）,TGF伪 and MPA were respectively detected by MTT assay,wound healing test and Western-blot method to observe the effects of TGF伪,MPA and TGF伪combined with MPA on proliferation,migration and motor ability of endometrial carcinoma Ishikawa cells,and the impact on expressions of CyclinD1 and E-cadherin. The influences of DMSO solvent on proliferation,migration and motor ability of endometrial carcinoma Ishikawa cells were also determined served as control. Results MTT assay showed that compared with control group,TGF伪 promoted proliferation of Ishikawa cells（ P 0. 05）,while MPA inhibited proliferation of Ishikawa cells（ P 0. 05）,and TGF伪 reduced the inhibition of MPA on Ishikawa cell.Wound healing test showed that Ishikawa cells could basically spread on the full scratching place in TGF伪 group,the MPA group and MPA combined with TGF伪 group,while Ishikawa cells didn＇t spread in the full scratching place in control group and MPA group. Western-blot method showed that the CyclinD1 expression increased while E-cadherin expression decreased in Ishikawa cells by the effect of TGF伪; MPA played reverse effect compared with TGF伪; the effect of TGF伪 combined with MPA and the effect of TGF伪 alone were corresponding. Conclusions TGF伪 can promote proliferation,migration and motor ability of endometrial carcinoma Ishikawa cells and antagonize the inhibitory effect of MPA,and its mechanism might be through up-regulation of CyclinD1 expression and the downregulation of E-cadherin expression. The increase of TGF伪 secretion can promote the occurrence of failure of progestin treatment in patients with endometrial carcinoma.