IL-11促进胃癌细胞增殖的机制研究

Study on mechanism of IL-11 facilitating the proliferation of gastric cancer cells

目的研究IL-11对胃癌细胞增殖的促进作用及其分子机制。方法将培养的BGG823胃癌细胞株随机分为干预组和对照组,对照组使用不含药物的DMEM进行处理,干预组采用含有20μg/L、50μg/L rh IL-11的DMEM进行处理。处理后24 h、48 h时,PI染色后采用流式细胞仪测定细胞周期中G0/G1、S期、G2/M期细胞所占比例,抽提RNA后采用荧光定量PCR测定细胞中PCNA、Cyclin D1、CDK4、MMP2、MMP9的m RNA含量。结果处理24 h、48 h后,干预组细胞中G0/G1细胞的比例明显低于对照组,S期和G2/M期细胞的比例明显高于对照组(P<0.05);50μg/L组细胞中G0/G1细胞的比例明显低于20μg/L组,S期和G2/M期细胞的比例显著高于20μg/L组(P<0.05);干预组细胞中PCNA、Cyclin D1、CDK4的m RNA含量明显高于对照组(P<0.05);50μg/L组细胞中PCNA、Cyclin D1、CDK4的m RNA含量明显高于20μg/L组(P<0.05);干预组细胞中MMP2、MMP9的m RNA含量明显高于对照组(P<0.05);50μg/L组细胞中MMP2、MMP9的m RNA含量明显高于20μg/L组(P<0.05);且均与干预时间呈依赖性关系(P<0.05)。结论 IL-11能够促进胃癌细胞的增殖以及细胞周期的发展,上调PCNA、Cyclin D1、CDK4、MMP2、MMP9的表达是IL-11发挥促增殖作用可能的分子机制。

Objective To investigate the effect and molecular mechanism of IL-11 facilitating the pro-liferation of gastric cancer cells. Methods BGG823 gastric cancer cell lines were randomly divided into treat-ment group and control group. The treatment group was stimulated by IL-11 with a concentration 20μg/L and 50μg/L respectively, and control group was cultured in DMEM media. PI staining was performed 24 hours and 48 hours after stimulation to measure the cell cycle （G0/G1, S and G2/M）. Fluorogenic quantitative PCR was adopted to measure the mRNA levels of PCNA, CyclinD1, CDK4, MMP2 and MMP9. Results At 24th and 48th hour after stimulation, the proportion of cells in G0/G1 phase in the treatment group was significantly lower than that in the control group, the proportions of cells in S phase and G2/M phase were significantly higher than those in the control group （P〈0.05）. The proportion of G0/G1 cells treated with 50μg/L rh IL-11 was significantly lower than that treated with 20μg/L rh IL-11, the ratio of S and G2/M cells was significantly higher than that of the 20μg/L group （P〈0.05）. The proportions of cells in S phase and G2/M phase were sig-nificantly higher than those treated with 20μg/L rh IL-11（P〈0.05）. The mRNA levels of PCNA, CyclinD1, and CDK4 in the treatment group were significantly higher than those in the control group （P〈0.05）. The mRNA levels of PCNA, CyclinD1 and CDK4 in the group treated with 50μg/L rh IL-11 were significantly higher than those in the group treated with 20μg/L rh IL-11 （P〈0.05）. The mRNA levels of MMP2 and MMP9 in the treatment group were significantly higher than those in the control group （P〈0.05）. The mRNA levels of MMP2 and MMP9 in the group treated with 50μg/L rh IL-11 were significantly higher than those treated with 20μg/L rh IL-11（P〈0.05）. All of the above results show a time-depend relationship （P〈0.05）. Conclusion IL-11 can facilitate the proliferation and cell cycle progress of gastric cancer cells, and the possi-ble molecular mechanism is up-regulating the expression of PCNA, CyclinD1, CDK4, MMP2, and MMP9.