TNP-470对肺腺癌细胞增殖和凋亡的影响

The effect of TNP-470 on the proliferation and apoptosis of lung adenocarcinoma cells

目的 探讨TNP 4 70对肺腺癌细胞增殖和凋亡的影响及其作用机制。方法 以不同浓度的TNP 4 70作用于培养的肺腺癌AGZY 82A细胞株 ,以免疫组化S P法检测肺腺癌细胞增殖细胞核抗原 (PCNA)、p5 3、bcl 2、血管内皮生长因子 (VEGF)和VEGF受体Flk 1的表达。结果 随着TNP 4 70浓度的增加 ,肺腺癌细胞VEGF、Flk 1、PCNA的表达减少 ,p5 3、bcl 2的表达逐渐增加 ;当TNP 4 70为 10 7μg/L时 ,细胞增殖几乎停止。随着TNP 4 70 (10 4μg/L)作用时间的延长 ,肺腺癌细胞VEGF、Flk 1、PCNA的表达逐渐减少 ,而p5 3、bcl 2的表达逐渐增加。结论 TNP 4 70通过使肺腺癌细胞自分泌VEGF减少 ,Flk表达降低 ,从而抑制肺腺癌细胞增殖 ,促进其凋亡。

Objective To investigate the effect of TNP 470 on the proliferation and apoptosis of lung adenocarcinoma cells and to explore the mechanism of the effect. Methods The TNP 470 with different concentrations was added to cultured lung adenocarcinoma cell strain AGZY 82A and the expressions of proliferating cell nuclear antigen(PCNA), p53, bcl 2, vascular endothelial growth factor(VEGF) and VEGF receptor Flk 1 of the tumor cells were assessed by immunohistochemical methods. Results The experimental data showed that TNP 470 inhibit the expressions of VEGF and Flk 1 by tumor cells with dose dependence. In the group of cells without TNP 470(control group) the expression could rates of VEGF and Flk 1 were 70.42% and 50%,respectively; while in the group of cells with 10 7 μg/L TNP 470, the expression rates of VEGF and Flk 1 decreased to 13.2% and 7.2%, respectively. Under the lnfluence of 10 4 μg/L TNP 470, the expression rates of VEGF, Flk 1 by the tumor cells decreased gradually with prolonging of the action time. After 6 hours of action, the expression rate of VEGF decreased to 14.4% and after 12 hours, the expression rate of Flk 1 decreased to 6.2%. In the control group the proliferation rate of PCNA marked cells was (87.03±0 75)% and the positive expression rate of p53 marked cells was (3.67±0 39)%, while in the 10 7 μg/L TNP 470 group the proliferation rate and positive rate of p53 marked cells were 0 and (63.28±0 84)%,respectively. No expression of bcl 2 in both control and low concentration TNP 470 group. Its expression increased gradually as the concentration induced. In the 10 4 μg/L TNP 470 group the expression of PCNA by tumor cells decreased. But the expression of p53, bcl 2 increased gradually with prolonging of the action time. Conclusion TNP 470 could inhibit the proliferation and promote the apoptosis of lung adenocarcinoma cells through reduction of the VEGF autocrine and down regulation of the VEGF receptor.