Abstract
Pseudomonas aeruginosa-mannose-sensitive hemagglutinin (PA-MSHA) has demonstrated efficacy against several solid tumors. In this study, we found that PA-MSHA inhibited the proliferation of PANC-1 and SW1990 pancreatic cancer cells, but had no obvious effects on HPDE6-C7 normal human pancreatic duct epithelial cells. Electron microscopy revealed the presence of apoptotic bodies and intracellular vacuole formation in PA-MSHA-treated pancreatic cancer cells. Flow cytometric analysis indicated the rate of apoptosis correlated with the PA-MSHA concentration. We observed a decrease in cell fractions in G0/G1 and G2/M phases, and an increase in the fraction in S phase (p < 0.01). PA-MSHA thus caused cell cycle arrest. Increasing concentrations of PA-MSHA did not alter total levels of EGFR, AKT or ERK, but levels of the corresponding phosphoproteins decreased. PA-MSHA also reduced tumor volume in a xenograft mouse model of pancreatic cancer (p < 0.01). Furthermore, caspase-3 levels decreased while the levels of cleaved caspase-3 increased (p < 0.01). These data suggest that by blocking cell cycle progression, PA-MSHA induces apoptosis and inhibits tumor growth. PA-MSHA-mediated inhibition of EGFR signaling and activation of the caspase pathway may play an important role in the induction of apoptosis in pancreatic cancer cells.
Highlights
Pancreatic cancer is a malignant neoplasm of the digestive system
We found that Pseudomonas aeruginosa-mannose-sensitive hemagglutinin (PA-MSHA) inhibited the proliferation of PANC-1 and SW1990 pancreatic cancer cells, but had no obvious effects on HPDE6-C7 normal human pancreatic duct epithelial cells
We analyzed the effects of PA-MSHA on the proliferation of pancreatic cancer and normal ductal epithelial cell lines using CCK-8 assays
Summary
Pancreatic cancer is a malignant neoplasm of the digestive system. The median survival time of pancreatic cancer patients is 3–6 months and the 5-year survival rate is less than 5%. Gemzar (gemcitabine) single-agent chemotherapy is the standard treatment for metastatic or locally advanced pancreatic cancer, but it has a modest survival benefit [5,6]. FOLFIRINOX, a combination of chemotherapeutic agents (folinic acid, fluorouracil, irinotecan, and oxaliplatin), was recently shown to nearly double the median survival of pancreatic ductal adenocarcinoma (PDAC) patients compared to gemcitabine (11.1 vs 6.8 months). NPT in combination with gemcitabine resulted in a median survival time of 8.5 months compared to 6.7 months after gemcitabine treatment alone [8,9]. Given the moderate improvements in PDAC patient prognosis, there is an urgent requirement for novel therapeutic strategies to improve overall survival
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