상악동암에서 Sulindac Sulfide에 의한 세포소멸 기전

Abstract

Background and Objectives：Head and neck cancer is the sixth most common cancer in human body. Squamous cell cancer (SCC) accounts for most of sinonasal cancers. Prediction of cancer development and induction of cell death are thought to account for the conquest of maxillary sinus cancer. Little is known about its biochemical mechanism(s) of cell death. Recently, human epidemiological and clinical intervention indicate that nonsteroidal anti-inflammatory drugs (NSAIDs) and the cyclooxygenase (COX) inhibitor have chemopreventive activity against colorectal cancer. We examined what kind of NSAIDs induce death of maxillary sinus cancer cells.

Materials and Method：Human maxillary sinus cancer cells were treated with NSAIDs. The NSAIDs-induced cell death was measured by Flow cytometry (FACS). To know whether sulindac sulfide-induced cell death is apoptosis or necrosis, we carried out Western blot analysis using anti-poly ADP-ribosyl polymerase (PARP) IgG and caspase 3 assay. We also measured cell survival rate using general caspases inhibitor, Z-VAD-fmk.

Results：Treatment of human maxillary sinus cancer cells with sulindac sulfide resulted in a dose-dependent cell death, and induction of apoptosis. General caspases inhibitor, Z-VAD-fmk potentiated the apoptosis inhibitory effect of sulindac sulfide.

Conclusion：These results suggest that the inhibition of caspases is responsible for a part of the induction of apoptosis by sulindac sulfide. Inhibition of caspase 3 activity may, therefore, be a useful biochemical target for the development of chemopreventive and chemotherapeutic drugs for maxillary sinus cancer.