The association between p53 protein phosphorylation at serine 15, serine 20 and sensitivity of cells isolated from patients with ovarian cancer and cell lines to chemotherapy in in vitro study.

Abstract

The association between p53 protein phosphorylated at serine 15 (Ser15), serine 20 (Ser20) and ovarian tumor cell sensitivity after chemotherapy was analyzed in order to define the influence of p53 activation on tumor cell sensitivity to chemotherapy. The study was performed on ovarian cancer cell line (OvBH-1), colon adenocarcinoma metastasis to ovary (SW626) and on cells isolated from ascitic fluids from patients with ovarian cancer: with (p53+) or without (p53-) p53 nuclear protein accumulation. p53 protein, Ser15, Ser20, Bax, Noxa and PgP protein expression was evaluated by means of immunocytochemical staining before and after chemotherapy. Cell viability after treatment was estimated using MTT assay. Cell lines and tumor cells p53+, p53- revealed a significant decrease in cell survival after camptothecin, paclitaxel, cisplatin treatment, compared to the control group (p < 0.01). In p53+ group, the expression of Ser20 significantly increased after camptothecin and paclitaxel (p < 0.05). Ser15, Ser20, Bax, Noxa expression correlated with MTT and depended on p53+, p53- tumor cell and the drug used (p < 0.05). Expression of Bax and Noxa were dependent on the type of tumor cells and drug used. The correlation between Ser15, Ser20 and Bax, Noxa expression was found in cell lines and tumor cells (p < 0.05). Our study suggests that the relation between Ser15 or Ser20 and tumor cell viability might reflect their role in tumor sensitivity on chemotherapy in dependent p53 protein status. Revealed association between p53 protein phosphorylated at Ser15, Ser20 and Bax, Noxa protein expression determined the apoptotic activity of tumor cells.