[Effect of exogenous p73 gene on chemosensitivity of wild-type p53 human lung adenocarcinoma cell A549].
摘要
BACKGROUND: To assess the effects of exogenous p73 gene on chemosensitivity of wild-type p53 human lung adenocarcinoma cell A549 to cisplatin (DDP) and adriamycin (ADM). METHODS: Recombinant eukaryotic expression vector pcDNA3 containing full-length human wild-type p73α cDNA or p53 cDNA was transfected into A549 cells which had wtp53 by lipofectamine-mediated gene transfection. The chemosensitivity of tumor cells to DDP and ADM was observed before and after transfection. RESULTS: A549-p73α could stably express P73α protein. The P73α protein expression was significantly increased in A549-p73α than that in A549 and A549-pcDNA3. The growth and colony formation of A549-p73α were significantly inhibited compared with A549, A549-pcDNA3 and A549-wtp53. Flow cytometry and DNA fragmentation analysis showed apoptosis of A549-p73α cells was significantly increased. The IC₅₀ values for DDP and ADM were reduced to approximate 1/6 and 1/70 in A549-p73α cells compared with A549 cells respectively.. CONCLUSIONS: Exogenous p73 gene is capable of enhancing the sensitivity of wild-type p53 human lung adenocarcinoma cell A549 to chemotherapeutic drugs. It is probably for p73 to be used in the treatment of p53-resistant tumors.