X射线对人肝癌血管内皮细胞迁移的影响及其机制
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摘要
目的探讨X射线对人肝癌血管内皮细胞(TEC)迁移的影响并探讨其机制。方法细胞划痕实验检测TEC细胞迁移能力,实时荧光PCR法检测Plk1 mRNA表达水平,免疫印迹法检测Plk1、STAT3及磷酸化STAT3(p-STAT3Y705)水平。结果 2 Gy X射线照射后24 h TEC迁移距离为(114.37±35.12)像素,对比未受照射TEC迁移距离(78.89±24.67)显著升高(P<0.01);2 Gy X射线照射后Plk1 mRNA表达水平显著升高(P<0.05),BI2536抑制Plk1激酶活性后p-STAT3Y705水平降低;2 Gy X射线照射后Plk1和p-STAT3Y705水平显著升高。结论 2 Gy X射线通过Plk1磷酸化STAT3(而非增加STAT3表达水平)来发挥其促进TEC迁移作用。
Objective To investigate the effect of X-ray irradiation on migration of human hepatocellular carcinoma tumor-derived endothelial cells(TEC)and its mechanism.Methods Migration test of TECs was detected by wound healing assay. The expression level of Plk1 mRNA was detected by quantitative real-time PCR and the levels of Plk1, STAT3 and phosphorylated STAT3 were assayed by Western Blot.Results The migrationdistance of 2 Gy group was(114.37±35.12)Pixel in 24 h,which was significantly higher than that of control group(78.89±24.67)(P<0.01).Compared with the control group,the expression level of Plk1 mRNA increased significantly in 2 Gy dose group(P<0.05).The expression level of p-STAT3 Y705 decreased after the activity of Plk1 was inhibited by BI2536.The levels of Plk1 and p-STAT3 Y705 increased significantly after 2 Gy X-ray irradiation.Conclusion The results indicated that 2 Gy X-ray irradiation promotes the migration of TEC through activation of STAT3 phosphorylation modulated by Plk1 instead of increasing the expression level of STAT3..
Objective To investigate the effect of X-ray irradiation on migration of human hepatocellular carcinoma tumor-derived endothelial cells(TEC)and its mechanism.Methods Migration test of TECs was detected by wound healing assay. The expression level of Plk1 mRNA was detected by quantitative real-time PCR and the levels of Plk1, STAT3 and phosphorylated STAT3 were assayed by Western Blot.Results The migrationdistance of 2 Gy group was(114.37±35.12)Pixel in 24 h,which was significantly higher than that of control group(78.89±24.67)(P<0.01).Compared with the control group,the expression level of Plk1 mRNA increased significantly in 2 Gy dose group(P<0.05).The expression level of p-STAT3 Y705 decreased after the activity of Plk1 was inhibited by BI2536.The levels of Plk1 and p-STAT3 Y705 increased significantly after 2 Gy X-ray irradiation.Conclusion The results indicated that 2 Gy X-ray irradiation promotes the migration of TEC through activation of STAT3 phosphorylation modulated by Plk1 instead of increasing the expression level of STAT3..
引文
[1] Shanmugam M K,Warrier S,Kumar A P,et al.Potential role of natural compounds as anti-angiogenic agents in cancer[J].Curr Vasc Pharmacol,2017,15(6):503-519.
[2] 吴晔,王震侠.肝细胞癌血管生成及抗血管生成治疗的研究进展[J].肝胆胰外科杂志,2014,26(1):78-82.
[3] Combes G,Alharbi I,Braga L G,et al.Playing polo during mitosis:PLK1 takes the lead[J].Oncogene,2017,36(34):4819-4827
[4] Chen J L,Chen J P,Huang Y S,et al.Radiosensitization in esophageal squamous cell carcinoma:Effect of polo-like kinase 1 inhibition[J].Strahlenther Onkol,2016,192(4):260-268.
[5] Furtek S L,Backos D S,Matheson C J,et al.Strategies and approaches of targeting STAT3 for cancer treatment[J].ACS Chem Biol,2016,11(2):308-318.
[6] Vilalta M,Rafat M,Graves E E.Effects of radiation on metastasis and tumor cell migration [J].Cell Mol Life Sci,2016,73(16):2999-3007.
[7] Li T,Zeng Z C,Wang L,et al.Radiation enhances long-term metastasis potential of residual hepatocellular carcinoma in nude mice through TMPRSS4-induced epithelial-mesenchymal transition[J].Cancer Gene Ther,2011,18(9):617-626.
[8] 闫位娟,李伟,李峰生,等.microRNA-424-5p对电离辐射的A549细胞侵袭和迁移能力的影响[J].中国辐射卫生,2017,26(2):129-132,141.
[9] Wu J G,Ivanov A I,Fisher P B,et al.Polo-like kinase 1 induces epithelial-to-mesenchymal transition and promotes epithelial cell motility by activating CRAF/ERK signaling[J].Elife,2016,5:e10734.
[10] 于慧杰,吴晔,李峰生,等.敲低Plk1对人肝癌血管内皮细胞迁移影响研究[J].中华肿瘤防治杂志,2015,22(8):584-587.
[11] Zhang Y,Du X L,Wang C J,et al.Reciprocal activation between PLK1 and Stat3 contributes to survival and proliferation of esophageal cancer cells[J].Gastroenterology,2012,142(3):521-530.
[2] 吴晔,王震侠.肝细胞癌血管生成及抗血管生成治疗的研究进展[J].肝胆胰外科杂志,2014,26(1):78-82.
[3] Combes G,Alharbi I,Braga L G,et al.Playing polo during mitosis:PLK1 takes the lead[J].Oncogene,2017,36(34):4819-4827
[4] Chen J L,Chen J P,Huang Y S,et al.Radiosensitization in esophageal squamous cell carcinoma:Effect of polo-like kinase 1 inhibition[J].Strahlenther Onkol,2016,192(4):260-268.
[5] Furtek S L,Backos D S,Matheson C J,et al.Strategies and approaches of targeting STAT3 for cancer treatment[J].ACS Chem Biol,2016,11(2):308-318.
[6] Vilalta M,Rafat M,Graves E E.Effects of radiation on metastasis and tumor cell migration [J].Cell Mol Life Sci,2016,73(16):2999-3007.
[7] Li T,Zeng Z C,Wang L,et al.Radiation enhances long-term metastasis potential of residual hepatocellular carcinoma in nude mice through TMPRSS4-induced epithelial-mesenchymal transition[J].Cancer Gene Ther,2011,18(9):617-626.
[8] 闫位娟,李伟,李峰生,等.microRNA-424-5p对电离辐射的A549细胞侵袭和迁移能力的影响[J].中国辐射卫生,2017,26(2):129-132,141.
[9] Wu J G,Ivanov A I,Fisher P B,et al.Polo-like kinase 1 induces epithelial-to-mesenchymal transition and promotes epithelial cell motility by activating CRAF/ERK signaling[J].Elife,2016,5:e10734.
[10] 于慧杰,吴晔,李峰生,等.敲低Plk1对人肝癌血管内皮细胞迁移影响研究[J].中华肿瘤防治杂志,2015,22(8):584-587.
[11] Zhang Y,Du X L,Wang C J,et al.Reciprocal activation between PLK1 and Stat3 contributes to survival and proliferation of esophageal cancer cells[J].Gastroenterology,2012,142(3):521-530.