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目的:观察乏氧射线双调控的TK腺病毒载体-Ad.HRE.CArG.HSV-TK对体外培养的乳腺癌细胞Bcap37和MDA-MB-435生长和凋亡的影响。方法:MTT法检测腺病毒转导联合放疗对常氧(37℃,19%O2,5%CO2)和乏氧(37℃,0.1%O2,5%CO2)状态下细胞的生长抑制作用,Annexin V-FITC染色检测细胞凋亡。结果:HSV-TK/GCV系统对乳腺癌细胞具杀伤效应和旁观者效应,Bcap37和MDA-MB-435细胞对GCV的IC50分别为9.09和7.83μg/mL。常氧状态下腺病毒载体(Ad)与放疗(RT)联用组(Ad+RT)细胞生长抑制率和凋亡率明显高于Ad组和相应同等剂量放疗组(P<0.05),对Bcap37和MDA-MB-435细胞的增敏比(SER)均为1.55。乏氧和(或)放疗处理后,乏氧+Ad+RT组抑制率明显高于常氧+Ad+假照射组和常氧+Ad+RT组,P<0.05。结论:Ad.HRE.CArG.HSV-TK腺病毒载体联合放疗可显著抑制乳腺癌细胞生长并诱导凋亡,为进一步开展乳腺癌的基因-放射治疗研究奠定了基础。
OBJECTIVE: To observe the effect of hypoxia-regulated TK adenovirus vector -Ad.HRE.CArG.HSV-TK on the growth and apoptosis of Bcap37 and MDA-MB-435 cells in vitro. Methods MTT assay was used to detect the effect of adenovirus transduction combined with radiotherapy on the growth of cells under normoxia (37 ℃, 19% O2, 5% CO2) and hypoxia (37 ℃, 0.1% O2, 5% V-FITC staining was used to detect apoptosis. Results: HSV-TK / GCV system had killing effect and bystander effect on breast cancer cells. The IC50 of Bcap37 and MDA-MB-435 cells to GCV were 9.09 and 7.83 μg / mL, respectively. The growth inhibition rate and apoptosis rate of adenovirus vector (Ad) and radiotherapy (RT) combined with normoxia were significantly higher than that of Ad group and the same dose of radiotherapy (P <0.05) And the sensitization ratio (SER) of MDA-MB-435 cells were both 1.55. After hypoxia and / or radiotherapy, the inhibition rate in hypoxia + Ad + RT group was significantly higher than that in normoxia + Ad + sham group and normoxia + Ad + RT group (P <0.05). Conclusion: Ad.HRE.CArG.HSV-TK adenovirus vector combined with radiotherapy can significantly inhibit the growth of breast cancer cells and induce apoptosis, which lays the foundation for the further study of gene-radiation therapy in breast cancer.