TGF-β1对胃癌细胞和多药耐药胃癌细胞抗增殖作用及其机制的探讨

Anti-proliferation effect and its mechanism of TGF-β1 on gastric carcinoma and drug-resistant gastric carcinoma cells

目的:探讨TGF-β1对胃癌细胞和多药耐药胃癌细胞增殖的影响及其机制。方法:采用MTT法、RT-PCR和酶联吸附反应检测24、48和72h的细胞生存抑制率、C-myc基因的表达和端粒酶活性。结果:在24、48和72h时TGF-β1处理的实验组SNU-601细胞生存抑制率分别为(18.66±1.37)%、(21.19±1.55)%和(31.51±1.71)%,SNU-601/cis10细胞生存抑制率分别为(38.90±2.56)%、(50.00±2.61)%和(50.38±1.86)%,各时间段与对照组相比,生存抑制率均显著增高,P值均为0.000;实验组多药耐药胃癌细胞生存抑制率与胃癌细胞相比明显增高,P均<0.05。RT-PCR测定结果,TGF-β1可时间依赖性抑制C-myc基因的表达和端粒酶活性,与对照组相比均明显降低,P均<0.05。端粒酶活性检测结果,TGF-β1时间依赖性抑制端粒酶活性,与对照组相比均明显降低,P均<0.05,对多药耐药胃癌细胞的端粒酶活性抑制作用更明显,在48和72h时端粒酶活性呈阴性,在各时间段与实验组胃癌细胞相比差异均有统计学意义,P均<0.05。结论:TGF-β1对SNU-601胃癌细胞及SNU-601/cis10多药耐药胃癌细胞具有抗增殖作用,并对多药耐药胃癌细胞的抑制作用更明显,其机制之一与抑制C-myc基因的表达及端粒酶活性有关。

OBJECTIVE： To investigate the proliferation effect and its mechanism of TGF-β1 on gastric carcinoma and drug resistant gastric carcinoma cells. METHODS： The cell survival inhibitory rates at 24 h, 48 h and 72 h, C-myc gene expression, and the telemerase activity were detected by using MTT, RT-PCR, and ELISA methods, respectively. RESULTS： In the TGF-β1 treatment group, the cell survival inhibitory rates at 24 h, 48 h and 72 h were （18.66±1.37） %, （21.19±1.55）% and （31.51± 1.71）% on SNU-601 cells, and （38.90±2.56）%, （50.00± 2.61）% and （50.38± 1.86）% and on SNU-601/cis10 cells, respectively, and significantly increased compared with the control group, P = 0.000. RTPCR assay showed TGF-β1 inhibited C-myc gene expression in the experiment group in a time-dependent manner, which showed a significant difference between the experimental and control groups,P〈0.05. In addition, the telomerase activity assay showed TGF-β1 inhibited the telomerase activity in the experiment group in a time-dependent manner, which showed a significant difference between the experimental and control groups, and especially it had the inhibition effect on resistant gastric carcinoma cells, and there was no any activity of telomerase at 48 h and 72 h. There was a significant difference between gastric carcinoma cells and resistant gastric carcinoma cells, P〈 0.05. CONCLUSIONS： TGF-β1 could inhibit the proliferation of SNU-601 gastric carcinoma and SNU 601/cis10 drug resistant gastric carcinoma cells, and especially has the inhibition effect on the resistant gastric carcinoma cells. The inhibitory effect of TGF-β1 might be correlated with the C-myc gene expression and the activity of telomerase.