文章摘要
周小晖,贡叶清,刘晓蓉,林 凡.帕博西尼和厄洛替尼联合治疗结直肠癌的协同作用及其机制[J].南京医科大学学报,2021,(8):1121~1127
帕博西尼和厄洛替尼联合治疗结直肠癌的协同作用及其机制
Combination of palbociclib and erlotinib exhibits synergistic antitumor effect in colorectal cancer
投稿时间:2021-03-03  
DOI:doi:10.7655/NYDXBNS20210803
中文关键词: 结直肠癌  帕博西尼  厄洛替尼  异种移植模型
英文关键词: colorectal cancer  palbociclib  erlotinib  patient⁃derived xenograft
基金项目:国家自然科学基金(81672962)
作者单位
周小晖 南京医科大学细胞生物学系江苏 南京 211166 
贡叶清 南京医科大学细胞生物学系江苏 南京 211166 
刘晓蓉 南京医科大学细胞生物学系江苏 南京 211166 
林 凡 南京医科大学细胞生物学系江苏 南京 211166 
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中文摘要:
      目的:评估帕博西尼(Palbociclib)单独或联合表皮生长因子缀体抑制剂厄洛替尼(Erlotinib)治疗结直肠癌(colorectal cancer,CRC)的有效性。方法:采用Alamar blue法和克隆形成实验检测帕博西尼单独或联合厄洛替尼对CRC细胞系增殖的影响;采用DNA含量定量法检测细胞周期分布变化;分别通过β?半乳糖苷酶和DCFH?DA染色检测细胞衰老和活性氧积累的情况;通过Western blot分析相关蛋白表达水平;在CRC患者来源异种移植模型中检测联合治疗的效果。结果:帕博西尼单独治疗有效抑制CRC细胞增殖,诱导细胞G1期阻滞、细胞衰老和胞内活性氧积累。帕博西尼和厄洛替尼联合治疗CRC具有协同作用,厄洛替尼进一步增强帕博西尼对CRC的多种抑制效应和多信号通路抑制,在CRC患者来源的异种移植模型中显示出了良好的协同抑制作用。结论:帕博西尼联合厄洛替尼在体外和体内能够协同抑制结直肠癌的生长。
英文摘要:
      Objective:This stndy aims to evaluate the efficacy of palbociclib alone or in combination with the epidermal growth factor receptor inhibitor erlotinib in the treatment of colorectal cancer(CRC). Methods:Alamar bule method and clone formation assay were used to detect the effects of palbociclib alone or in combination with erlotinib on the proliferation of CRC cell lines. Cell cycle distribution was determined by DNA content. Cell senescence and reactive oxygen species (ROS) accumulation were detected by β?galactosidase and DCFH?DA staining. The expression levels of related proteins were analyzed by Western blot and their clinical efficacies were evaluated in CRC patient?derived xenograft models. Results:Palbociclib inhibits CRC cell proliferation,induce G1 cell arrest,cell senescence and intracellular ROS accumulation effectively. Combination of palbociclib and erlotinib exhibits synergistic effects on CRC,and erlotinib further enhances the multiple inhibitory effects and multi?signaling pathway inhibition of palbociclib on CRC. Synergistic inhibition was also shown in CRC patient?derived xenograft models. Conclusion:Palbociclib combined with erlotinib synergistically inhibits the growth activity of colorectal cancer in vitro and in vivo.
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