Induction of chemosensitivity in human lung cancer cells in vivo by adenovirus-mediated transfer of the wild-type p53 gene.
Induction of chemosensitivity in human lung cancer cells in vivo by adenovirus-mediated transfer of the wild-type p53 gene.
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发表时间：
1994-05
期刊：
影响因子：
11.2
通讯作者：
T. Fujiwara;E. A. Grimm;T. Mukhopadhyay;Wei-wei Zhang;Laurie B. Owen-Schaub;J. Roth
中科院分区：
文献类型：
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作者：
T. Fujiwara;E. A. Grimm;T. Mukhopadhyay;Wei-wei Zhang;Laurie B. Owen-Schaub;J. Roth
重组腺病毒介导的野生型p53基因转移到单层培养或多细胞肿瘤球体的人非小细胞肺癌细胞系H358，其中有一个纯合缺失的p53，显着增加这些细胞的敏感性化疗药物顺铂。经处理的细胞发生凋亡，并伴有特异性DNA片段化。将p53-腺病毒构建体直接注射到H358肿瘤s.c.植入nu/nu小鼠，随后腹膜内给予顺铂，诱导肿瘤的大量凋亡破坏。这些结果支持了使用复制缺陷型野生型p53腺病毒和DNA损伤药物进行基因置换联合治疗人类癌症的方案的临床应用。
Recombinant adenovirus-mediated transfer of the wild-type p53 gene into monolayer cultures or multicellular tumor spheroids of human non-small cell lung cancer cell line H358, which has a homozygous deletion of p53, markedly increased the cellular sensitivity of these cells to the chemotherapeutic drug cisplatin. Treated cells underwent apoptosis with specific DNA fragmentation. Direct injection of the p53-adenovirus construct into H358 tumors s.c. implanted into nu/nu mice, followed by i.p. administration of cisplatin, induced massive apoptotic destruction of the tumors. These results support the clinical application of a regimen combining gene replacement using replication-deficient wild-type p53 adenovirus and DNA-damaging drugs for treatment of human cancer.