Oncotarget

Research Papers:

Palbociclib inhibits epithelial-mesenchymal transition and metastasis in breast cancer via c-Jun/COX-2 signaling pathway

Ge Qin, Fei Xu, Tao Qin, Qiufan Zheng, Dingbo Shi, Wen Xia, Yun Tian, Yanlai Tang, Jingshu Wang, Xiangshen Xiao, Wuguo Deng and Shusen Wang _

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Oncotarget. 2015; 6:41794-41808. https://doi.org/10.18632/oncotarget.5993

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Abstract

Ge Qin1,*, Fei Xu1,*, Tao Qin1,*, Qiufan Zheng1, Dingbo Shi1, Wen Xia1, Yun Tian1, Yanlai Tang2, Jingshu Wang1, Xiangshen Xiao1, Wuguo Deng1, Shusen Wang1

1Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, Guangzhou 510060, China

2Department of Pediatrics, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou 510080, China

*These authors contributed equally to this work

Correspondence to:

Shusen Wang, e-mail: [email protected]

Wuguo Deng, e-mail: [email protected]

Keywords: palbociclib, breast cancer, metastasis, epithelial-mesenchymal transition, COX-2

Received: July 20, 2015     Accepted: October 05, 2015     Published: October 19, 2015

ABSTRACT

Palbociclib, a highly selective CDK4/6 inhibitor, has been shown to be a novel anti-tumor agent that suppresses breast cancer cell proliferation. However, its anti-metastasis activity remains controversial. In the present study, we evaluated whether palbociclib prevented breast cancer cell metastasis and revealed its regulatory mechanism. We found that palbociclib inhibited migration and invasion in the breast cancer cells MDA-MB-231 and T47D. The epithelial-mesenchymal transition (EMT) markers, vimentin and Snail, were down-regulated with palbociclib treatment. Moreover, we revealed that this inhibition was mediated by the c-Jun/COX-2 pathway. COX-2 was decreased after palbociclib treatment. The production of PGE2 was also reduced along with COX-2. Additionally, our data showed that c-Jun, a crucial transcriptional regulator of COX-2, was down-regulated by palbociclib. We found that palbociclib weakened the COX-2 promoter binding activity of c-Jun and prevented its translocation from the cytoplasm to cell nuclei. Bioluminescence imaging and tail intravenous injection were used to evaluate the anti-metastasis effect of palbociclib in vivo. The data demonstrated that palbociclib reduced breast cancer metastasis to the lung. These results therefore demonstrated that the anti-metastasis activity of palbociclib is mediated via the c-Jun/COX-2 signaling pathway by inhibiting EMT in breast cancer cells.


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