[Effects of exogenous wild-type p53 gene expression on sensitivity to chemotherapeutic agents in human lung cancer...

To investigate the effects of exogenous wild-type p53 (wtp53) gene expression on sensitivity to chemotherapeutic agents with different mechanism of action in human lung cancer cells.

A human lung cancer cells line 801-D with point mutation of p53 was transfected with either constructed recombinant plasmid pEGFP-p53 , which expressed wtp53 or pEGFP vector. The expression of neo and wtp53 gene in anti-G418 clone , 801-D vector and 801-D-wtp53 , were detected by PCR. The functional activity of transfected wtp53 was demonstrated by partly 801-D apoptosis. 3 H-TdR uptake assay was taken for drug sensitivity measure according to standard procedures. Flow cytometry was employed to determine cell death.

Sensitivity of 801-D-wtp53 to cisplatin and 5-fluorouracil was higher than that of 801-D vector by 9. 7 and 11. 4 fold respectively. There was no significant difference for other DNA-damaging agents and non-DNA-damaging agents , such as etoposide and adriamycin , vincristine and methylenum Caeruleum. Analysis of DNA ladder by gel electrophoresis and morphological observation showed cell necrosis characteristics.

801-D cell line shows a selective sensitization to DNA-damaging agents when exogenous wtp53 is expressed. The increased sensitivity to cisplatin by exogenous wtp53 expression may be through non-apoptosis pathway. This study results provide experimental bases for comprehensive treatment of lung cancer.