中国肿瘤生物治疗杂志2024,Vol.31Issue(12):1218-1226,9.DOI:10.3872/j.issn.1007-385x.2024.12.007
低剂量辐射联合人端粒酶逆转录酶C27过表达治疗非小细胞肺癌的实验研究
Experimental study on low-dose radiation combined with hTERTC27 overexpression for the treatment of non-small cell lung cancer
摘要
Abstract
Objective:To investigate the effects of low-dose radiation(LDR)combined with human telomerase reverse transcriptase C-terminal polypeptide 27(hTERTC27)overexpression on the proliferation and apoptosis of lung cancer A549 cells,and to observe the in vivo antitumor effects of LDR combined with C27.Methods:The pEgr-hTERTC27 plasmid was transfected into human non-small cell lung cancer(NSCLC)A549 cells and mouse Lewis lung carcinoma(LLC)cells.Cells stably expressing C27(A549-C27 and LLC-C27)were screened by G418 selection.The cells were divided into six groups:conventional radiation(CONV-RT)group(A549-Con),LDR group(A549-Low),C27 group(A549-C27),CONV-RT combined with C27 group(A549-C27-Con),LDR combined with C27 group(A549-C27-Low),and control group(A549-Mock).The irradiation dose in LDR group was only 36%of CONV-RT group.MTT assay was used to detect cell proliferation,and flow cytometry was used to measure cell apoptosis.LLC cell-transplanted tumor model in mice was established through subcutaneous implantation,and the animal experiment groups were similar with cell experiments.Tumor growth,volume,and mass were recorded in each group.Muscle infiltration near the transplanted tumors was observed using H-E staining.Results:Compared with A549-Mock group,the proliferative activity of A549-Con and A549-Low group was significantly decreased(all P<0.01).Furthermore,the proliferation activity of A549-C27-Con and A549-C27-Low cells was significantly lower than that of A549-C27 cells(all P<0.01).Compared with A549-Mock,the apoptosis rates were significantly higher in A549-Con and A549-Low groups(P<0.01);however,no significant difference in apoptosis rates were observed among A549-C27,A549-C27-Con and A549-C27-Low groups(all P>0.05).In tumor-bearing mice,both CONV-RT and LDR significantly reduced tumor mass compared with unirradiated mice(all P<0.01).In addition,the tumor mass and local infiltration were significantly reduced in both LLC-C27-Low and LLC-C27-Con groups.Conclusion:LDR combined with C27 achieves similar antitumor effects to CONV-RT alone while reducing the total radiation dose in NSCLC.Moreover,LDR and C27 peptide synergize in their anti-tumor effects,with their combination reducing local tumor infiltration in transplanted tumor models.关键词
低剂量辐射/人端粒酶逆转录酶C末端多肽27/基因治疗/非小细胞肺癌Key words
low-dose radiation(LDR)/human telomerase reverse transcriptase C-terminal polypeptide 27(hTERTC27)/gene therapy/non-small cell lung cancer(NSCLC)分类
医药卫生引用本文复制引用
周洪帅,林桂淼,王晓梅,罗琳,杨柳,卞东圆,李沙沙,蒋圣哲,陈强..低剂量辐射联合人端粒酶逆转录酶C27过表达治疗非小细胞肺癌的实验研究[J].中国肿瘤生物治疗杂志,2024,31(12):1218-1226,9.基金项目
内蒙古自治区自然科学基金(No.2021SHZR0996) (No.2021SHZR0996)
包头市青年创新人才项目资助 ()