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Pseudomonas aeruginosa-mannose-sensitive hemagglutinin inhibits pancreatic cancer cell proliferation and induces apoptosis via the EGFR pathway and caspase signaling.

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.

SUBMITTER: Cheng X

PROVIDER: S-EPMC5363631 | biostudies-literature | 2016 Nov

REPOSITORIES: biostudies-literature

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Pseudomonas aeruginosa-mannose-sensitive hemagglutinin inhibits pancreatic cancer cell proliferation and induces apoptosis via the EGFR pathway and caspase signaling.

Cheng Xi X Wang Bingrui B Jin Zhijian Z Ma Ding D Yang Weiping W Zhao Ren R Jing Xiaoqian X Shen Baiyong B Peng Chenghong C Qiu Weihua W

Oncotarget 20161101 47

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 r ...[more]

PMID: 27788491

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Project description:PurposeMetastatic breast cancer (MBC) remains an incurable disease despite major therapeutic advances. Pseudomonas aeruginosa-mannose-sensitive hemagglutinin (PA-MSHA) has been established to have anti-proliferative effects against breast cancer cells in preclinical experiments, and is indicated for treatment of cancer in China. We performed a phase II trial combining PA-MSHA with capecitabine in patients with heavily pretreated MBC.MethodsEligibility criteria included human epidermal growth factor receptor 2-negative MBC, prior therapy with anthracyclines and taxanes, at least one prior chemotherapy regimen for metastatic disease or early relapse after a taxane plus anthracycline adjuvant regimen, and adequate organ function and performance status. PA-MSHA 1 mg was administered subcutaneously every other day and capecitabine 1000 mg/m2 orally twice a day for 2 weeks on, 1 week off. The primary end point was progression-free survival.ResultsA total of 97 patients were enrolled. Median progression-free survival (PFS) was 4.0 months [95 % confidence interval (CI) 3.0-4.9], which was not significantly different from that in historical controls. However, median PFS was significantly longer (8.2 months; 95 % CI 6.7-9.7) in 24 patients with moderate immune-related adverse events (irAEs) such as fever or skin induration at the injection site than in those with no or mild irAEs (3.1 months, 95 % CI 2.5-3.6; p = 0.003). Overall survival was also improved in these patients (25.4 vs. 16.4 months; p = 0.044). PA-MSHA has a good safety profile, with only 6 patients (6.2 %) discontinuing treatment. PA-MSHA did not increase capecitabine-related toxicities such as hand-foot syndrome, nausea, and vomiting.ConclusionAdding PA-MSHA to capecitabine has a good safety profile in patients with heavily pre-treated MBC, although benefit from this regimen might occur only in patients with moderate PA-MSHA-related adverse events.Trial registrationClinicalTrials.gov NCT01380808.

Dataset Information

Pseudomonas aeruginosa-mannose-sensitive hemagglutinin inhibits pancreatic cancer cell proliferation and induces apoptosis via the EGFR pathway and caspase signaling.

Publications

Pseudomonas aeruginosa-mannose-sensitive hemagglutinin inhibits pancreatic cancer cell proliferation and induces apoptosis via the EGFR pathway and caspase signaling.

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