摘要
目的验证节拍化疗治疗非小细胞肺癌的疗效和安全性,并进一步探索其抗肿瘤分子机制。方法构建小鼠肺癌皮下瘤模型并分为节拍化疗组和安慰剂组(阴性对照组)给药,记录小鼠体重及肿瘤大小变化情况;治疗结束后,收集小鼠血液进行血常规及生化检查,收集小鼠肿瘤组织进行免疫组化染色及转录组测序。结果节拍化疗可延缓肺癌生长,节拍化疗组肿瘤组织明显小于安慰剂组;血常规及血生化相关指标检测结果显示,安慰剂组红细胞(RBC)、白细胞(WBC)数量以及丙氨酸氨基转移酶(ALT)、天冬氨酸氨基转移酶(AST)和血肌酐(Scr)含量分别为(6.97±0.41)×10^(12)/L、(13.26±0.29)×10^(9)/L、(33.33±2.51)U/L、(235.33±57.62)U/L、(20.67±2.08)μmol/L,与节拍化疗组(6.87±0.66)×10^(12)/L、(12.59±2.27)×10^(9)/L、(38.67±3.79)U/L、(225.33±6.81)U/L、(20.33±3.79)μmol/L比较差异均无统计学意义(t=0.509、0.209、2.032、0.299、0.134,P=0.638、0.845、0.112、0.780、0.900)。小鼠肝脏、肾脏、脾脏及肺组织HE染色均未观察到明显的炎性浸润和病理改变。转录组分析筛选出68个差异表达基因,差异基因功能主要与信号转导及免疫相关,KEGG通路富集分析涉及多条信号通路,主要包括转化生长因子β(TGF-β)信号通路、白介素-17(IL-17)信号通路和肿瘤坏死因子(TNF)等信号通路。结论节拍化疗治疗非小细胞肺癌安全且有效,主要可通过TGF-β信号通路、IL-17信号通路和TNF等多条信号通路调控肿瘤生长。
Objective To assess the effectiveness and safety of beat chemotherapy in treating non-small cell lung cancer,and to investigate its anti-tumor molecular mechanism.Methods In this study,we developed a subcutaneous tumor model of lung cancer in mice.The mice were subsequently divided into two groups:the beat chemotherapy group and the placebo group(negative control group).Throughout the treatment period,we monitored the changes in body weight and tumor size of the mice.At the conclusion of the treatment,we collected blood samples from the mice to conduct blood routine and biochemical examinations.Furthermore,we obtained tumor tissues from the mice to perform immunohistochemical staining and sequencing of the transcriptome.Results The study found that beat chemotherapy could effectively delay the growth of lung cancer.The tumor tissues in the beat chemotherapy group were significantly smaller compared to the placebo group.The results of routine blood and blood biochemistry tests showed that the levels of red blood cells(RBCs),white blood cells(WBCs),alanine aminotransferase(ALT),aspartate aminotransferase(AST)and blood creatinine(Scr)were similar between the placebo group and the beat chemotherapy group.The values for RBCs,WBCs,ALT,AST and Scr in the placebo group were(6.97±0.41)×10^(12)/L,(13.26±0.29)×10^(9)/L,(33.33±2.51)U/L,(235.33±57.62)U/L and(20.67±2.08)μmol/L,respectively.The corresponding values in the beat chemotherapy group were(6.87±0.66)×10^(12)/L,(12.59±2.27)×10^(9)/L,(38.67±3.79)U/L,(225.33±6.81)U/L and(20.33±3.79)μmol/L.Statistical analysis showed no significant differences between the two groups(t=0.509,0.209,2.032,0.299,0.134,P=0.638,0.845,0.112,0.780,0.900).Furthermore,there were no signs of inflammatory infiltration or pathological changes in the liver,kidney,spleen,and lung tissues of the mice.Transcriptome analysis identified 68 differentially expressed genes,which were mainly associated with signal transduction and immunity.Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis revealed the involvement of several signaling pathways,including the transforming growth factorβ(TGF-β)signaling pathway,the interleukin-17(IL-17)signaling pathway,and the tumor necrosis factor(TNF)signaling pathway.Conclusions The use of chemotherapy has been proven to be safe and effective in treating non-small cell lung cancer.It primarily functions by regulating tumor growth through various signaling pathways,including the TGF-βsignaling pathway,IL-17 signaling pathway,and TNF.
作者
王雪
马亚锐
张琪
高佳仪
袁月
何柳儿
李琳
Wang Xue;Ma Yarui;Zhang Qi;Gao Jiayi;Yuan Yue;He Liuer;Li Lin(Peking University Fifth School of Clinical Medicine,Beijing 100730,China;Department of Cell Biology and Molecular Biology,National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital,Chinese Academy of Medical Science and Peking Union Medical College,Beijing 100021,China;Department of Medical Oncology,Beijing Hospital,National Center of Gerontology Institute of Geriatric Medicine,Chinese Academy of Medical Sciences,Beijing 100730,China)
出处
《中华老年医学杂志》
CAS
CSCD
北大核心
2024年第3期342-347,共6页
Chinese Journal of Geriatrics
基金
中国医学科学院医学与健康科技创新工程项目(2021-12M-1-012)。
关键词
癌
非小细胞肺
抗肿瘤联合化疗方案
化学疗法
辅助
转化生长因子Β
Carcinoma,non-small-cell lung
Antineoplastic combined chemotherapy protocols
Chemotherapy,adjuvant
Transforming growth factor beta
