Effect of difluoromethylorithine proliferation, apoptosis and cell cycle in different breast cell lines with different ODC G316A

Abstract

Objective To investigate the proliferation, apoptosis and cell cycle and possible mechanisms of different breast cell lines by difluoromethylorithine (DMFO). Methods The growth of breast cancer MDA-435 (ODC GG) cell lines and SK-br3 (ODC AA) cell lines treated with DFMO were observed. The apoptosis and cell cycle were detected by flow cytometry. PCR was applied to detect the changes of A and G alleles of ODC G316A in MCF-7 cells treated with DFMO. Results The growth inhibition rates of MDA-435 and SK-br3 cells treated with 10 mmol/L and 20 mmol/L DFMO after 48 h were 24.1 % and 33.6 %, 46.3 % and 53.5 %, respectively, and there was statistical significance (t=2.134, P=0.021, t=2.213, P=0.019). The growth inhibition rates of MDA-435 and SK-br3 treated with 10 mmol/L and 20 mmol/L DFMO after 72 h were 28.9 % and 35.7 %, 54.3 % and 65.4 %, respectively, and there was statistical significance (t=2.434, P=0.015, t=2.489, P=0.013). The apoptosis rates of MDA-435 (ODC GG) and SK-br3 (ODC AA) cells both dealt with 20 mmol/L of DFMO after 24 h, 48 h and 72 h were (7.58±2.06) % and (13.88±3.45) % (t=2.047, P=0.041), (43.28±14.28) % and (59.96±16.42) % (t=3.680, P=0.000), (77.87±30.25) % and (93.08±32.15) % (t=3.293, P=0.000 1), respectively. The proportions of S stage cells MDA-435 (ODC GG) and SK-br3 (ODC AA) cells under the same condition after 24 h, 48 h and 72 h were (13.25±2.38) % and (12.89±2.21) % (P>0.05), (21.43±3.12) % and (12.24±3.55) % (t=2.638, P=0.012), (16.32±3.23) % and (15.24±3.01) % (P>0.05), respectively. After the treatment by DFMO, the expression of ODC G316A allele A in breast cancer cell line MCF-7 (ODC AG) was reduced (t=3.708, P=0.000), and the expression of G had no significant changes. Conclusion The proliferation inhibition and apoptosis in breast cancer cells treated by DFMO is different in breast cancer cells with different genetic type of ODC G316A. DFMO can inhibit the activity of ODC, and the mechanism may be that DFMO could selectively bind to ODC G316A allele A. Key words: Breast neoplasms; Ornithine decarboxylase G316A; Polymorphism; Difuromethylornithine