Additive effects of Cox-1 and Cox-2 inhibition on breast cancer in vitro.

ABSTRACT

We hypothesized that combined treatment with Cox-1 and Cox-2 specific inhibitiors would exhibit synergistic effects against breast cancer in vitro. Two human breast cancer cell lines (HTB26, MCF-7) were treated with catechin (Cox-1 inhibitor) or NS398 (Cox-2 inhibitor) at 100 microM as both single and combined treatments. Reductions in cell growth were observed in both cell lines at 24 and 72 h in both single and combined treatments (p<0.001). Combined treatment produced a significantly greater inhibition as compared to single agents alone. Upon cell cycle evaluation, Cox-1 and -2 antagonism increased G1 and G2 phase fractions in MCF-7 cells (p<0.001 and p<0.05 respectively). No additive changes were observed when the two agents were combined. An increase in the G2 phase was observed in the HTB26 cells when treated with NS398 alone (p<0.001). However, a decrease in the S-phase was observed when these cells were treated with NS398, as a single agent (p<0.01) or when the two agents were combined (p<0.01). The significant and additive effects exhibited by the combination of Cox-1 and -2 inhibitors and their effects on cell cycle suggest that these agents could become an effective treatment modality for carcinoma of the breast.