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Eerimental study on low-dose radiation combined with hTERTC27 overexpression for the treatment of non-small-cell lung cancer
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Abstract:
[Abstract] Objective: To investigate the effects of low-dose radiation (LDR) combined with human telomerase reverse transcriptase Cterminal 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.
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