Enhanced induction of Bax gene expression in H460 and H1299 cells with the combined treatment of cisplatin and adenovirus mediated wt-p53 gene transfer.

Ji Hyung Choi,Kwang Sung Ahn,Young Sook Hong,Jhingook Kim

doi:10.1038/emm.2000.5

Ji Hyung Choi, Kwang Sung Ahn + Show 2 more

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https://doi.org/10.1038/emm.2000.5

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Journal: Experimental and Molecular Medicine	Publication Date: Mar 1, 2000
Citations: 28	License type: cc-by

Affiliation: Ewha Womans University

Abstract

Cytotoxic effect of either cisplatin or p53 gene transfection of lung cancer cells may be different depending on the p53 status of cells. We investigated cytotoxic effects on the combined treatment of cisplatin and adenovirus mediated p53 gene transfer (Avp53) in both H460 and H1299 cells in vitro. The results showed the highest numbers of apoptotic cells in both H460 and H1299 cells following the combined treatment regardless of p53 status in comparison with either cisplatin or Avp53 alone. The expression levels of p53, p21, Bax and ICE were examined to understand a possible cellular signal path of the combined treatment. In western analyses, the patterns of phosphorylated p53 protein were different between Avp53 and combined treatment. The expressions of p21 and Bax were increased in combined treatment, whereas the cleaved form of ICE (20 kD) was not detected. These results suggest that cisplatin induced p53 protein phosphorylation and may activate the downstream of p53 gene expression such as p21 and Bax. The enhanced apoptosis of lung cancer cells by the combined treatment may be useful in the development of clinical therapeutic modality of lung tumors.

Highlights

Cisplatin-based chemotherapy has been frequently used for an advanced lung cancer
Cytotoxic effect of cisplatin in lung cancer cells in vitro To investigate the role of p53 for cisplatin-treated lung cancer cells, we examined the cytotoxicity of cisplatin in H460 cells expressing wt-p53 and H1299 cells having null p53
H460 cells were more sensitive to cisplatin than H1299 cells suggesting that the overexpression of p53 by cisplatin treatment could lead to apoptotic pathways

Summary

Introduction

Induction of p53 expression in lung cancer cells treated with cisplatin triggers apoptotic pathway. When p53 is expressed in cancer cells, it has to be phophorylated in order to induce expressions of the downstream of p53 genes such as p21 and Bax. The expressions of p21 and Bax induce the apoptotic pathways. Cisplatin could induce apoptosis via p53 independent apoptotic pathway in cancer cells with alterations of p53 (Wang et al, 1997). To overcome the difficulties in cisplatin treatment of lung cancer cells with alteration of p53, p53 gene therapy, as an alternative method, has been introduced. As shown in previous data, the cytotoxic effect of Avp depends on p53 status of lung cancer cells (Kim et al, 1997). We concluded that cytotoxic effect of either cisplatin or Avp treatment depends on the status of p53

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