Abstract |
To identify more therapeutic targets and clarify the detailed mechanisms of Pseudomonas aeruginosa- mannose-sensitive hemagglutinin (PA-MSHA) on breast cancer cells both in vitro and in vivo. PA-MSHA was administered to epidermal growth factor receptor (EGFR)-positive human breast cancer cell lines MDA-MB-231HM and MDA-MB-468 in vitro and to mice bearing tumor xenografts. The mannose cocultured test was used to detect the effect of mannose on PA-MSHA-induced cell proliferation, cell cycle arrest, apoptosis, and EGFR pathway signaling. We found that cells stimulated with PA-MSHA exhibited a downregulation of EGFR signaling. The addition of mannose partially inhibited the PA-MSHA-stimulated cell anti-proliferative effect, cell apoptosis, cell cycle arrest, activation of apoptosis-associated caspases, and even downregulation of the EGFR signaling pathway. In vivo, PA-MSHA treatment significantly suppressed mammary tumorigenesis in xenografts in mice and decreased lung metastasis in MDA-MB-231HM cell-transplanted mice. Tumor sample analyses confirmed inhibition of the EGFR pathway in the PA-MSHA-treated mice. In conclusion, this study showed that the involvement of the mannose-mediated EGFR pathway has a critical function in the preclinical rationale for the development of PA-MSHA for the treatment of human breast cancer. It also suggests the potentially beneficial use of PA-MSHA in adjuvant therapy for breast tumors with EGFR overexpression.
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Authors | Z-B Liu, Y-F Hou, J Zhu, D-L Hu, W Jin, Z-L Ou, G-H Di, J Wu, Z-Z Shen, Z-M Shao |
Journal | Oncogene
(Oncogene)
Vol. 29
Issue 20
Pg. 2996-3009
(May 20 2010)
ISSN: 1476-5594 [Electronic] England |
PMID | 20228837
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Hemagglutinins
- RNA, Messenger
- RNA, Small Interfering
- EGFR protein, human
- ErbB Receptors
- Mannose
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Topics |
- Animals
- Apoptosis
(drug effects)
- Blotting, Western
- Breast Neoplasms
(metabolism, pathology, prevention & control)
- Cell Adhesion
(drug effects)
- Cell Line, Tumor
- Cell Proliferation
(drug effects)
- Enzyme-Linked Immunosorbent Assay
- ErbB Receptors
(antagonists & inhibitors, genetics, metabolism)
- Female
- Fimbriae, Bacterial
(metabolism)
- Flow Cytometry
- Hemagglutinins
(pharmacology)
- Humans
- Lung Neoplasms
(metabolism, prevention & control, secondary)
- Mannose
(metabolism)
- Mice
- Mice, Inbred BALB C
- Mice, Nude
- Neoplasm Transplantation
- Pseudomonas aeruginosa
(metabolism)
- RNA, Messenger
(genetics, metabolism)
- RNA, Small Interfering
(pharmacology)
- Reverse Transcriptase Polymerase Chain Reaction
- Signal Transduction
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