TGF-β_1对胃癌和耐药性胃癌细胞株的生长抑制与p53和cyclin D1蛋白相关性研究

Effect of TGF-β_1 on cell growth inhibition in gastric carcinoma and drug-resistant gastric carcinoma cell lines and relationship with P53 and cyclin D1 protein expression

目的通过已建立的耐药性胃癌细胞株模型,探讨TGF-β1对胃癌细胞及耐药性胃癌细胞株的生长抑制作用与P53和cyclinD1蛋白相关关系的研究。方法利用MTT、Westernblot方法检测细胞生长抑制率、P53和cyclinD1蛋白的表达水平。结果TGF-β1明显抑制SNU-601/WT和SNU-601/cis2细胞的生长,与对照组相比具差异有显著性(P<0.01),同时,对SNU-601/cis2细胞的抑制率与SNU-601/WT细胞相比,48和72h时明显增高(P<0.05)。Westernblot结果,TGF-β1可时间依赖性抑制P53蛋白的表达,与对照组相比差异具有显著性(P<0.01)。而对cyclinD1蛋白的表达,在SNU-601/cis2细胞中24和48h有明显抑制作用(P<0.01)。结论TGF-β1抑制SNU-601/WT细胞及SNU-601/cis2细胞的生长,在耐药性胃癌细胞中其抑制作用更明显。其抑制作用可能与抑制P53蛋白的表达有关;同时,在耐药性胃癌细胞株中早期可抑制cyclinD1蛋白的表达。

[Obejctive] To investigate the effect of TGF-β1 on the cell growth inhibition in gastric carcinoma and drug-resistant gastric carcinoma cell lines and the relationship with P53 and cyclin D1 protein expressions by using the drug-resistant gastric carcinoma cell line models, [Methods] The cell growth inhibitory rate and P53 and cyclin D1 protein expressions were detected by using MTT and Western blot assay, respectively, [Results] The cell growth inhibitory rate of TGF-β1 was increased along with the time process in SNU-601/WT and SNU-601/cis2 cell lines. The inhibitory rate in control group was significantly higher at an.y stage than in the experimental group （P 〈0.01）. And there was significant difference at 48 h and 72 h between drug resistant cell line and gastric carcinoma cell line （SNU-601/WT） （P 〈0.05）. Western blot assay showed the TGF-β1 could inhibit P53 protein expression of SNU-601/ WT and SNU-601/cis2 cells in a time-dependent manner, it showed significant difference between experimental and control group （P 〈0.01）. Cyclin D1 protein expression was evidently inhibited at 24 h and 48 h in SNU-601/cis2 cells （P 〈0.01）. [Conclusions] TGF-β1 could inhibit the growth of SNU-601/WT gastric cancer and SNU-601/cis2 drug resistant cell lines. The mechanism was related with the inhibition of P53 protein expression. And TGF-β1 could inhibit cyclin D1 expression in the early stage of SNU-601/cis2 drug resistant cell line.