- 作者: Shinn-Liang Lai; Reury-Perng Perng; Jaulang Hwang
- 作者服務機構: Chest Department, Veterans General Hospital-Taipei, Department of Intermal Medicine, School of Medicine, National Yang-Min University and Institute of Molecular Biology, Academia Sinica, Taipei, Taiwan, ROC
- 中文摘要: --
- 英文摘要: This study examined the effects of p53 gene status onDNA damage-induced cell death and chemosensitivitytovarious chemotherapeutic agents in non-small cell lungcancer (NSCLC) cells. A mutant p53 gene was introducedinto cells carrying the wild-type p53 gene and also viceversa to introduce the wild-type p53 gene into cells carry-ing the mutant p53 gene. Chemosensitivity and DNAdamage-induced apoptosis in these cells were then ex-amined. This study included five cell lines, NCI-H1437,NCI-H727, NCI-H441 and NCI-H1299 which carry a mu-tant p53 gene and NCI-H460 which carries a wild-typep53 gene. Mutant p53-carrying cells were transfectedwith the wild-type p53 gene, while mutant p53 geneswere introduced into NCI-H460 cells. These p53 geneswere individually mutated at amino acid residues 143,175, 248 and 273. The representative cell line NCI-H1437cells transfected with wild-type p53 gene (H1437/wtp53)showed a dramatic increase in susceptibility to threeanticancer agents (7-fold to cisplatin, 21-fold to etopo-side, and 20-fold to camptothecin) compared to untrans-fected or neotransfected H1437 cells. An increase in che-mosensitivity was also observed in wild-type p53 trans-fectants of H727, H441, H1299 cells. The results of che-mosensitivity were consistent with the observations onapoptotic cell death. H1437/wtp53 cells, but not H1437parental cells, exhibited a characteristic feature of apop-totic cell death that generated oligonucleosomal-sizedDNA fragments. In contrast, loss of chemosensitivity andlack of p53-mediated DNA degradation in response toanticancer agents were observed in H460 cells trans-fected with mutant p53. These observations suggest thatthe increase in chemosensitivity was attributable to wild-type p53 mediation of the process of apoptosis. In addi-tion; our results also suggest that p53 gene status modu-lates the extent of chemosensitivity and the induction ofapoptosis by different anticancer agents in NSCLC cells.
- 中文關鍵字: --
- 英文關鍵字: --