Inhibition of integrin β1 decreases the malignancy of ovarian cancer cells and potentiates anticancer therapy via the FAK/STAT1 signaling pathway.

Abstract

Integrin β1 (ITGB1) is frequently upregulated in ovarian cancer, and promotes ovarian tumorigenesis and cancer progression. However, the effects of ITGB1 inhibition on ovarian cancer progression and anticancer therapy remain to be elucidated. The results of the present study indicated that ITGB1 was upregulated in HO‑8910 and HO‑8910PM ovarian cancer cell lines, and knockdown of ITGB1 using short hairpin RNA markedly increased tumor cell apoptosis, decreased tumor cell adhesion and migration, and reduced tumor cell invasion by suppressing matrix metalloproteinase (MMP)‑2 and MMP‑9 expression. Furthermore, the results of the present study provided evidence regarding the role of ITGB1 inhibition in bevacizumab anticancer therapy. The activation of signal transducer and activator of transcription 1 (STAT1) by focal adhesion kinase (FAK) is involved in integrin‑mediated cell migration and adhesion. In the present study, the expression levels of FAK were markedly upregulated in ovarian cancer. The adherence and migratory potentials of ovarian cancer cells were significantly reduced when the FAK/STAT1 signaling pathway was inhibited by fludarabine. The results of the present study demonstrated that ITGB1 inhibition effectively reduced tumorigenesis and disease exacerbation, and contributed to bevacizumab anticancer therapy via the FAK/STAT1 signaling pathway, suggesting that inhibition of ITGB1 is a potential novel therapeutic strategy for ovarian carcinogenesis.

• Authors: Lei Zhang, Wen Zou
• Journal: Molecular medicine reports (Mol Med Rep) Vol. 12 Issue 6 Pg. 7869-76 (Dec 2015) ISSN: 1791-3004 [Electronic] Greece
• PMID: 26497667 (Publication Type: Journal Article)

Chemical References

• Antineoplastic Agents
• Integrin beta1
• Bevacizumab
• Focal Adhesion Kinase 1
• PTK2 protein, human
• Vidarabine
• fludarabine

Topics

• Antineoplastic Agents (pharmacology)
• Apoptosis (drug effects)
• Bevacizumab (therapeutic use)
• Cell Adhesion (drug effects, genetics)
• Cell Line, Tumor
• Cell Movement (drug effects, genetics)
• Disease Progression
• Drug Synergism
• Female
• Focal Adhesion Kinase 1 (genetics, metabolism)
• Gene Expression Regulation, Neoplastic
• Humans
• Integrin beta1 (genetics)
• Neoplasm Invasiveness
• Ovarian Neoplasms (drug therapy, genetics, pathology)
• Signal Transduction (drug effects)
• Vidarabine (analogs & derivatives, pharmacology)