Protein levels of p21, p27, cyclin E and Bax predict sensitivity to cisplatin and paclitaxel in head and neck squamous cell carcinomas

Abstract

Regression of tumor mass by chemotherapy is caused by growth suppression and/or apoptosis of tumor cells. Therefore, expression levels of cell cycle molecules and apoptosis should be predictive markers for the efficacy of a drug. In the present study, the relationship between expression of molecules in the cell cycle and apoptosis and chemosensitivity was investigated in head and neck squamous cell carcinoma cell lines. Expression of p53, p21, p27, cyclin D1, cyclin E, and Bax in 17 such cell lines were analyzed by Western blot analysis. The concentrations of four chemotherapeutic agents (cisplatin, 5-FU, vincristine, and paclitaxel) resulting in 50% cell growth inhibition were calculated as IC50 values for each cell line. Cell cycle analysis was performed using a FACScan flow cytometer. Cells with strong expression of p21, p27, or Bax showed significantly higher sensitivity to cisplatin, and cells with strong expression of Bax or weak expression of cyclin E showed significantly higher sensitivity to paclitaxel. Cisplatin most effectively killed cells expressing both p21 and p27 or either at G1 phase. Though the assessments of p21, p27, Bax, and cyclin E expression in tumor tissues have been reported to be useful as prognostic factors in head and neck squamous cell carcinoma, these correlations might not only describe the malignant biological behavior of the tumor, but also the response to chemotherapy. Furthermore, p21/p27 expression might be a useful guide for the choice of chemotherapeutic agents.