Differential response of oesophageal carcinoma cells to 5-fluorouarcil, cisplatin and taxol

Aims: Anticancer agents mediate cell death by activating elements of the apoptosis program. This study assesses the effect of the chemotherapeutic agents 5-fluorouracil, cisplatin and taxol on cell growth, apoptosis and levels of p53 and bcl-2 proteins in oesophageal carcinoma cells.

Methods: Human oesophageal adenocarcinoma (OE-33) and squamous cell carcinoma (OE-21) was used. Mutation in the p53 gene (exons 5–8) was determined by DNA sequencing. P53, bcl-2, bax and bcl-x proteins were detected by western blotting. LM-PCR was used to determine the biochemical feature of the apoptotic cells.

Results: This study identified a mutation in the p53 gene at codon 135 in OE-33 cells, whereas, OE-21 cells showed normal sequencing profile. Mutational status of p53 was associated with the chemosensitivity of oesophageal carcinoma cells to 5-fluorouracil. Both cisplatin and taxol induced apoptosis in oesophageal carcinomas with cisplatin selectively reducing the stability of the mutant p53 protein in adenocarcinoma cells. Induction of apoptosis by 5-fluorouracil, cisplatin and taxol was independent of bax and bcl-xl protein.

Conclusions: In vitro; the p53 gene status is sufficient to predict 5-fluorouracil sensitivity of oesophageal carcinoma cells. Cisplatin and taxol are inducers of apoptosis in oesophageal carcinoma cells, albeit via different molecular mechanisms.