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| 吉马酮调节FAK/YAP信号通路对非小细胞肺癌细胞顺铂耐药性的影响 |
| Effect of germarone modulating FAK/YAP signaling pathway on cisplatin resistance in non-small cell lung cancer cells |
| 投稿时间：2022-11-06 |
| DOI：10.3969/j.issn.1000-0399.2023.12.001 |
| 中文关键词: 吉马酮 局部黏着斑激酶/Yes相关蛋白通路 非小细胞肺癌 顺铂 耐药性 |
| 英文关键词: Germacrone Focal adhesion kinase/Yes-associated protein pathway Non-small cell lung cancer Cisplatin Drug resistance |
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| 中文摘要: |
| 目的 探讨吉马酮(GMC)调节局部黏着斑激酶(FAK)/Yes相关蛋白(YAP)通路对非小细胞肺癌(NSCLC)细胞顺铂(DDP)耐药性的影响。方法 将A549/DDP细胞分为CK组、低剂量GMC组(GMC-L组,5μmol/L)、中剂量GMC组(GMC-M组,10μmol/L)、高剂量GMC组(GMC-H组,20μmol/L)、GMC-H+pcDNA组(20μmol/L+转染pcDNA)、GMC-H+pcDNA-FAK组(20μmol/L+转染pcDNA-FAK)。检测各组细胞增殖、凋亡、迁移、侵袭情况;检测多药耐药基因1(MDR1)、增殖细胞核抗原(PCNA)、B淋巴细胞瘤-2(Bcl-2)、基质金属蛋白酶(MMP)-2、MMP-9、磷酸化的FAK(p-FAK)、YAP蛋白表达情况。结果 与CK组比较,GMC-L组、GMCM组、GMC-H组A549/DDP细胞OD450值、克隆形成率、划痕愈合率、侵袭细胞数、MDR1、PCNA、Bcl-2、MMP-2、MMP-9、p-FAK蛋白及核YAP蛋白表达降低,细胞凋亡率升高,且呈浓度依赖性(P<0.05);与GMC-H组、GMC-H+pcDNA组比较,GMC-H+pcDNA-FAK组A549/DDP细胞OD450值、克隆形成率、划痕愈合率、侵袭细胞数、MDR1、PCNA、Bcl-2、MMP-2、MMP-9、p-FAK蛋白及核YAP蛋白表达升高,细胞凋亡率降低(P<0.05)。结论 GMC可能通过抑制FAK/YAP信号通路减弱NSCLC细胞DDP耐药性。 |
| 英文摘要: |
| Objective To investigate the influence of germacrone(GMC) on cisplatin(DDP) resistance of non-small cell lung cancer(NSCLC) cells by regulating local focal adhesion kinase(FAK)/Yes-associated protein(YAP) pathway.Methods A549/DDP cells were separated into CK group, low-dose GMC group(GMC-L group, 5 μmol/L), medium-dose GMC group(GMC-M group, 10 μmol/L), and high-dose GMC group(GMC-H group, 20 μmol/L), GMC-H+pcDNA group(20 μmol/L+ transfected with pcDNA), and GMC-H+pcDNAFAK group(20 μmol/L+ transfected with pcDNA-FAK). CCK-8 method and plate cloning assay were applied to detect cell proliferation; flow cytometry was applied to detect apoptosis; scratch assay was applied to detect cell migration; Transwell was used to detect cell invasion; Western blot was applied to detect the expression of multidrug resistance gene 1(MDR1), proliferating cell nuclear antigen(PCNA), B celllymphoma-2(Bcl-2), matrix metalloproteinase(MMP)-2, MMP-9, phosphorylated FAK(p-FAK), YAP protein.Results Compared with the CK group,the OD450 value, clone formation rate, scratch healing rate, invasive cell number, the expression of MDR1, PCNA, Bcl-2, MMP-2, MMP-9, p-FAK protein and nuclear YAP protein of A549/DDP cells in the GMC-L group, GMC-M group and GMC-H group decreased, and the apoptosis rate increased, all in a concentration-dependent manner(P<0.05); compared with the GMC-H group and GMCH+pcDNA group, the OD450 value, clone formation rate, scratch healing rate, invasive cell number, the expression of MDR1, PCNA, Bcl-2, MMP-2, MMP-9, p-FAK protein and nuclear YAP protein of A549/DDP cells in the GMC-H+pcDNA-FAK group increased, and the apoptosis rate decreased(P<0.05).Conclusion GMC may attenuate DDP resistance of NSCLC cells by inhibiting FAK/YAP signaling pathway. |
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