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Kallistatin Suppresses Cell Proliferation and Invasion and Promotes Apoptosis in Cervical Cancer Through Blocking NF-κB Signaling

Tao Wang, Fan Shi, JiQuan Wang, Zi Liu, Jin Su

Department of Radiation Oncology, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, P.R. China

Oncology Research 2017, 25(5), 809-817. https://doi.org/10.3727/096504016X14799180778233

Abstract

Kallistatin has been recognized as an endogenous angiogenesis inhibitor and exerts pleiotropic effects in inhibiting tumor growth, migration, apoptosis, and inflammation. The purpose of the present study was to investigate the potential role and mechanisms of kallistatin in cervical cancer. We demonstrated that kallistatin effectively inhibited cell proliferation and enhanced apoptosis in a dose-dependent manner. Additionally, kallistatin suppressed migration and invasion activities and markedly reduced the expression of matrix-degrading metalloproteinases, progelatinase (MMP-2), MMP-9, and urokinase-type PA (uPA). Kallistatin reversed the epithelial–mesenchymal transition (EMT) and caused the upregulation of epithelial markers such as E-cadherin and inhibited mesenchymal markers such as N-cadherin and vimentin. Moreover, kallistatin led to a marked decrease in the expression of vascular endothelial growth factor (VEGF) and HIF-1a. In a xenograft mouse model, kallistatin treatment reduced tumor growth. Importantly, kallistatin strikingly impeded NF-kB activation by suppressing IkBa degradation and the level of phosphorylation of p65. Interestingly, similar to kallistatin, treatment with PDTC (an inhibitor of NF-kB) also attenuated cell invasion and migration. Taken together, these findings suggest that kallistatin suppresses cervical cancer cell proliferation, migration, and EMT and promotes cell apoptosis by blocking the NF-kB signaling pathway, suggesting that kallistatin may be a novel therapeutic target for cervical cancer treatment.

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APA Style
Wang, T., Shi, F., Wang, J., Liu, Z., Su, J. (2017). Kallistatin suppresses cell proliferation and invasion and promotes apoptosis in cervical cancer through blocking NF-κB signaling. Oncology Research, 25(5), 809-817. https://doi.org/10.3727/096504016X14799180778233
Vancouver Style
Wang T, Shi F, Wang J, Liu Z, Su J. Kallistatin suppresses cell proliferation and invasion and promotes apoptosis in cervical cancer through blocking NF-κB signaling. Oncol Res. 2017;25(5):809-817 https://doi.org/10.3727/096504016X14799180778233
IEEE Style
T. Wang, F. Shi, J. Wang, Z. Liu, and J. Su "Kallistatin Suppresses Cell Proliferation and Invasion and Promotes Apoptosis in Cervical Cancer Through Blocking NF-κB Signaling," Oncol. Res., vol. 25, no. 5, pp. 809-817. 2017. https://doi.org/10.3727/096504016X14799180778233



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