TRPM7的表达水平与肺癌发生发展的关系

Relationship between Expression Level of TRPM7 and Development of Lung Cancer

为了解TRPM7在肺癌中的表达及其与肺癌进展的关系,本研究检测了TRPM7在非小细胞肺癌患者肺癌组织样本和相邻正常肺泡组织样本中的表达,以及TRPM7在人肺腺癌A549细胞系和人支气管上皮细胞系16HBE中的表达。通过转染shRNA敲低肺癌细胞中的TRPM7,并应用TRPM7拮抗剂Waixenicin A处理细胞。免疫组化染色和Western blotting分析显示,与正常肺泡组织样本中的TRPM7表达相比,TRPM7在肺癌样本中显著高表达。TRPM7的表达水平与癌症分期有关,分期越高,TRPM7的表达水平越高。TRPM7在A549细胞中的表达强度显著高于16HBE细胞。细胞集落形成测定结果显示,沉默TRPM7会显著抑制细胞集落形成的能力。SRB细胞活力测定显示,沉默TRPM7会显著抑制细胞活力。沉默TRPM7显著降低了肺癌细胞的迁移(-68.94%)和侵袭(-68.84%)能力。沉默TRPM7显著抑制了热休克蛋白90α(HSP90α)、尿激酶型纤溶酶原激活剂(uPA)和基质金属蛋白酶2 (MMP2)的表达。Waixenicin A显著抑制了肺癌细胞的活力及Hsp90α/uPA/MMP2信号分子的表达。另外,Waixenicin A显著降低了肺癌细胞的迁移(-65.35%)和侵袭(-71.85%)能力。本研究表明,TRPM7的异常表达通过激活Hsp90α/uPA/MMP2信号通路来提高人肺癌细胞的活力和转移能力。研究结果表明,靶向TRPM7的抑制剂可能是治疗肺癌的有效药物。

In order to investigate the expression of TRPM7 in lung cancer and its relationship with the progress of lung cancer,this study examined the expression of TRPM7 in lung cancer tissue samples and adjacent normal alveolar tissue samples from patients with non-small cell lung cancer.And the expression of TRPM7 in human lung adenocarcinoma A549 cell line and human bronchial epithelial cell line 16 HBE were examined.TRPM7 in lung cancer cells was knocked down by transfection of sh RNA,and cells were treated with the TRPM7 antagonist Waixenicin A.Immunohistochemical staining and Western blotting analysis showed that TRPM7 was significantly overexpressed in lung cancer samples compared to normal alveolar tissue samples.The expression level of TRPM7 is related to cancer stage.The higher the stage,the higher the expression level of TRPM7.The expression intensity of TRPM7 in A549 cells was significantly higher than that of 16 HBE cells.The results of cell colony formation assay showed that silencing TRPM7 significantly inhibited the ability of cell colony formation.SRB cell viability assay showed that silencing TRPM7 significantly inhibited cell viability.Silencing TRPM7 significantly reduced the ability of lung cancer cells to migrate(-68.94%) and invade(-68.84%).Silencing TRPM7 significantly inhibited the expression of heat shock protein 90α(HSP90α),urokinase-type plasminogen activator(uPA) and matrix metalloproteinase 2(MMP2).Waixenicin A significantly inhibited the activity of lung cancer cells and the expression of Hsp90α/u PA/MMP2 signaling molecules.In addition,Waixenicin A significantly reduced lung cancer cell migration(-65.35%)and invasion(-71.85%) ability.This study demonstrates that aberrant expression of TRPM7 enhances the viability and metastasis of human lung cancer cells by activating the Hsp90α/u PA/MMP2 signaling pathway.The results of this research indicated that inhibitors,Inhibitors targeting TRPM7 may be effective drugs for the treatment of lung cancer.