Fujiwara T, Inoue F, Tanaka N
First Dept. of Surgery, Okayama University Medical School.
Gan To Kagaku Ryoho. 1998 Jan;25(2):194-200.
Molecular level approaches have demonstrated that tumor suppressor p53 gene, which is the most commonly mutated gene yet described in human cancers, plays an important role in the pathway of apoptosis triggered by DNA-damaging agents. In addition, defects in apoptosis caused by the inactivation of p53 resulted in resistance to treatment. Human gene therapy has become a reality with the development of effective techniques for delivering the gene to the target cells. These findings suggested a novel approach to cancer therapy with the direct delivery of wild-type p53 gene construct to cancer cells by using an adenoviral vector system. Restoration of wild-type p53 function markedly enhanced the antitumor effect of a common chemotherapeutic agent, cisplatin, in human non-small cell lung cancer cells as well as human colon cancer cells. The application of this technology to human cancer therapy is now in progress.
分子水平的研究方法表明,肿瘤抑制基因p53是人类癌症中最常发生突变的基因,在DNA损伤剂引发的细胞凋亡途径中起重要作用。此外,p53失活导致的细胞凋亡缺陷会产生治疗抗性。随着将基因传递到靶细胞的有效技术的发展,人类基因治疗已成为现实。这些发现提示了一种新的癌症治疗方法,即通过腺病毒载体系统将野生型p53基因构建体直接递送至癌细胞。野生型p53功能的恢复显著增强了常见化疗药物顺铂对人非小细胞肺癌细胞和人结肠癌细胞的抗肿瘤作用。该技术在人类癌症治疗中的应用正在进行中。