Oncotarget

Research Papers:

Bufalin enhances antitumor effect of paclitaxel on cervical tumorigenesis via inhibiting the integrin α2/β5/FAK signaling pathway

Fei Liu, Duo Tong, Haoran Li, Mingming Liu, Jiajia Li, Ziliang Wang _ and Xi Cheng

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Oncotarget. 2016; 7:8896-8907. https://doi.org/10.18632/oncotarget.6840

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Abstract

Fei Liu1,3,*, Duo Tong2,3,*, Haoran Li1,3,*, Mingming Liu1,3, Jiajia Li1,3, Ziliang Wang1,2,3 and Xi Cheng1,3

1 Department of Gynecologic Oncology and Cancer Institute, Fudan University Shanghai Cancer Center, Shanghai, China

2 Department of Medical Oncology, Fudan University Shanghai Cancer Center, Shanghai, China

3 Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China

* These authors have contributed equally to this work

Correspondence to:

Ziliang Wang, email:

Xi Cheng, email:

Keywords: cervical cancer, Bufalin, integrin α2/β5, FAK, paclitaxel

Received: August 01, 2015 Accepted: December 31, 2015 Published: January 07, 2016

Abstract

While Bufalin restrains primary tumorigenesis, the role of Bufalin in cervical cancer remains unclear. Here, we show that Bufalin can inhibit cervical cancer cell proliferation, block cell cycle in G2/M phase, induce cellular apoptosis and reduce cell metastasis through stimulation of p21waf/cip1, p27cip/kip, Bax and E-cadherin, and suppression of cyclin A, cyclin B1, CDK2, Bcl-2, Bcl-xl, MMP9 and SNAIL1. Further study suggests that Bufalin has no apparent damage to human normal cervical cells at the low concentration (<20nM), but increases the chemotherapeutic efficacy of paclitaxel. Mechanistic study reveals that Bufalin suppresses the integrin α2/FAK/AKT1/ GSK3β signaling. Finally, in vivo studies show that Bufalin blocks the Siha-induced xenograft tumor growth without detectable toxicity in the animals at the therapeutic doses, and the combination treatment of Bufalin and paclitaxel more efficiently inhibits xenograft tumor growth. Thus, Bufalin may be developed as a potential therapeutic agent to treat cervical cancer.


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