腹腔中由游离癌细胞分泌的TGF-β1影响腹膜间皮形态与功能进而促进癌转移的研究

Transforming growth factor beta1 produced by free cancer cells in peritoneal affect the function and morphology of mesothelial cells and promote peritoneal carcinomatosis

目的:研究胃癌分泌的转化生长因子-β1(TGF-β1)对腹膜的破坏机制及TGF-β1抑制剂对腹膜的保护。方法:ELISA法检测胃癌分泌上清中的相关细胞因子含量及在胃癌-腹膜相互作用中TGF-β-Smad信号通路蛋白的水平。观察TGF-β1抑制剂SB431542对腹膜癌转移的抑制作用。结果:5种胃癌细胞系均能分泌大量TGF-β1,TGF-β1的分泌量明显多于其他细胞因子。Western证实了TGF-β1及其信号通路TGF-β1/Smad 2、3参与胃癌对间皮的损伤。胃癌上清能破坏间皮层,致损伤脱落,与TGF-β1共培养能明显影响间皮细胞生长。TGF-β1抑制剂SB431542可阻止胃癌上清对间皮的损伤。结论:胃癌上清中TGF-β1高表达,影响腹膜间皮形态与功能进而促进了癌转移,机制可能与Smad信号通路有关。TGF-β1抑制剂能减轻胃癌上清对间皮的损伤。

Objective ：To investigate the effects of TGF - B on tumour - mesothelial interaction. Methods： The level of various soluble factors were mesured. The expressions of TGF - 13/Smad pathway related proteins were immu- nochemically evaluated. Results： The expression of TGF- B was significantly elevated in each gastric cancer cell line. Phosphorylated- Smad 2,3 expressions increased after gastric cancer cells treatment. Mesothelial cells exposed to gastric cancer cells became exfoliation and appeared injury,while blocking TGF - [31 partly inhibited these effects. Conclusion： TGF - B produced by cancer cells in peritoneal cavity affect the function and morphology of mesotheli- al cells so that the resuhing environment becomes favorable for peritoneal metastases. TGF - BSmad pathway may play an important role in above cascade. TGF - B inhibitor could partly inhibit these effects.