Expression of apolipoprotein C-1 in pancreatic cancer and its role in cell survival by avoiding apoptotic cell death

B31

The final goal of this study is developing new therapy against pancreatic cancer. Despite the recent advances of clinical managements, pancreatic cancer still remains one of the most lethal diseases with increasing incidence. This suggests that establishment of new target therapy is needed. For this purpose, we tried to identify a new serum factor highly expressed in pancreatic cancer patients, and examine if this new factor involves in pancreatic cancer development.To identify new serum factor in pancreatic cancer patients, we compared pre- and postoperative serum protein profiling obtained from patients with invasive pancreatic ductal carcinoma. Samples from twenty patients who underwent curative pancreatectomy were analyzed and we successfully identified 6630 Da protein, which is Apolipoprotein C-1 (ApoC-1), as more abundantly expressed in preoperative serum than in postoperative serum (p < 0.002). Next we examined whether ApoC-1 was expressed in pancreatic cancer tissues. RT-PCR analysis revealed abundant expression of ApoC-1 mRNA in pancreatic cancer tissue, but very low in adjacent normal pancreatic tissues (P<0.0001). Immunostaing of pancreatic cancer tissue also revealed the expression of ApoC-1 in cancer cells themselves, but not in normal pancreatic ductal cells which might pancreatic cancer arise from. To reveal the role of ApoC-1 in pancreatic cancer cells, we examined whether gene knockdown of ApoC-1 would affect the proliferation of pancreatic cancer cells. siRNA against ApoC-1 mRNA successfully inhibited the expression of ApoC-1 mRNA (more than 80% reduction) and protein in pancreatic cancer cell line, MIA PaCa II and AsPC-1. The treatment of MIA PaCa II and AsPC-1 with siRNA against ApoC-1 significantly reduced the cell proliferation and increased the number of dead cells compared with cells treated with negative control siRNA. Apoptosis membrane alteration assay (APOPercentage^™ Assay) revealed that treatment of siRNA against ApoC-1 induced apoptotic cell death in both cell lines.These data suggest that ApoC-1 in pancreatic cancer cells maintain cell proliferation by avoiding apoptotic cell death. The specific expression of ApoC-1 in pancreatic cancer tissue and its role in cell proliferation and preventing cells from spontaneous apoptosis suggest that ApoC-1 significantly contributes to the aggressiveness of pancreatic cancer and will be useful as a new therapeutic target for pancreatic cancer.