高良姜素调节MCP-1/CCR2信号轴对肺癌细胞恶性生物学行为的影响

Impact of galangin on the malignant biological behaviors of lung cancer cells by regulating the MCP-1/CCR2 signaling pathway

目的研究高良姜素通过调节单核细胞趋化蛋白-1(MCP-1)/趋化因子受体-2(CCR2)信号通路对肺癌细胞的恶性生物学行为产生的影响。方法将人肺癌细胞系A549分为ctrl组、低浓度高良姜素组(5μmol/L)、高浓度高良姜素组(100μmol/L)、吉非替尼组(10μmol/L)、高浓度高良姜素+MCP-1组(100μmol/L高良姜素+75 ng/mL MCP-1)。CCK-8试剂盒检测细胞活性;流式细胞术检测细胞凋亡;细胞划痕实验检测细胞迁移;transwell检测细胞侵袭能力;western blot检测MCP-1、CCR2、凋亡蛋白半胱氨酸蛋白酶(Caspase-3)、细胞增殖核抗原(Ki67)、基质金属蛋白酶2(MMP-2)蛋白表达。结果与ctrl组比较,低浓度高良姜素组、高浓度高良姜素组、吉非替尼组肺癌细胞A549的细胞存活率、细胞迁移愈合率、细胞侵袭数、MCP-1、CCR2、Ki67、MMP-2蛋白表达降低,而细胞凋亡率、Caspase-3含量升高(P<0.05);与高浓度高良姜素组比较,高浓度高良姜素+MCP-1组A549细胞存活率、细胞迁移愈合率、细胞侵袭数、MCP-1、CCR2、Ki67、MMP-2蛋白表达升高,而细胞凋亡率、Caspase-3含量降低(P<0.05)。结论高良姜素可能通过抑制MCP-1/CCR2信号通路进而抑制肺癌A549细胞恶性生物学行为,促进其凋亡。

Objective To study the impacts of galangin on the malignant biological behaviors of lung cancer cells by regulating monocyte chemoattractant protein-1(MCP-1)/CC chemokine receptor-2(CCR2)signaling pathway.Methods The human lung cancer cell line A549 was induced with blank control,low-dose galangin(5μmol/L),high-dose galangin(100μmol/L),10μmol/L gefitinib,or high-dose galangin+75ng/mL MCP-1.Cell viability,apoptosis,migration and invasion were detected by CCK-8 assay,flow cytometry,wound healing assay and Transwell assay,respectively.Protein expressions of MCP-1,CCR2,Caspase-3,Ki67 and matrix metalloproteinase-2(MMP-2)were detected by Western blot.Result Compared with those induced with blank control,A549 cells treated with low-dose galangin,high-dose galangin or gefitinib presented significantly lower cell survival rate,wound healing rate,invasive cell number and protein expressions of MCP-1,CCR2,Ki67 and MMP-2,but higher apoptotic rate and protein expression of Caspase-3(P<0.05).Compared with those induced with high-dose galangin,A549 cells treated with high-dose galangin+75ng/mL MCP-1 presented significantly higher cell survival rate,wound healing rate,invasive cell number and protein expressions of MCP-1,CCR2,Ki67 and MMP-2,but lower apoptotic rate and protein expression of Caspase-3(P<0.05).Conclusion Galangin may inhibit the malignant biological behaviors of lung cancer A549 cells and promote its apoptosis by inhibiting the MCP-1/CCR2 signaling pathway.