1.Experimental study on low-dose radiation combined with hTERTC27 overexpression for the treatment of non-small cell lung cancer
Hongshuai ZHOU ; Guimiao LIN ; Xiaomei WANG ; Lin LUO ; Liu YANG ; Dongyuan BIAN ; Shasha LI ; Shengzhe JIANG ; Qiang CHEN
Chinese Journal of Cancer Biotherapy 2024;31(12):1218-1226
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.
2.Effect of human telomerase reverse transcriptase C27 polypeptide over-expression on growth of transplanted nasopharyngeal carcinoma in nude mice
Guimiao LIN ; Hui LI ; Jiami LINLI ; Suxia LIN ; Shiming WU ; Xiaomei WANG
Cancer Research and Clinic 2014;26(2):94-97
Objective To investigate the effect of human telomerase reverse transcriptase C27 polypeptide (hTERTC27) over-expression on orthotopic implanted tumor growth which induced by nasopharyngeal carcinoma cells C666-1 in vivo.Methods Stably transfected C666-1 cell lines were used to establish subcutaneously transplanted tumor mouse model.The tumor growth was observed and the tumor growth curve was made by measuring the volumes of tumors every day.HE staining was used to observe the change of histomorphology.The expressions of cleaved Caspase-3,Caspase-9,PARP,bax and bcl-2 were detected by Western blot analysis.Results The in vivo mouse model showed that over-expression of hTERTC27 significantly reduced tumor volume and tumor weight (P < 0.05),and decreased the local muscle infiltration.Over-expression of hTERTC27 significantly up-regulated the expressions of cleaved Caspase-3,Caspase-9,PARP and bax (P < 0.01),and down-regulated the expression of bcl-2 (P < 0.01).Conclusion The results indicate that over-expression of hTERTC27 can obviously inhibit the growth of transplanted tumor in nude mice,which is possibly related to the regulation of bax and bcl-2 expression.

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