Oncotarget

Research Papers:

Physapubescin B inhibits tumorgenesis and circumvents taxol resistance of ovarian cancer cells through STAT3 signaling

Xiaofeng Zhao, Lu Huang, Wanwan Xu, Xiaoyan Chen, Yan Shen, Wenjie Zeng and Xiao Chen _

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Oncotarget. 2017; 8:70130-70141. https://doi.org/10.18632/oncotarget.19593

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Abstract

Xiaofeng Zhao1,2,*, Lu Huang1,*, Wanwan Xu1,3, Xiaoyan Chen1, Yan Shen1, Wenjie Zeng1 and Xiao Chen4

1Department of Gynecology, Zhejiang Provincial People's Hospital, Hangzhou, Zhejiang Province, China

2Key Laboratory of Tumor Molecular Diagnosis and Individualized Medicine of Zhejiang Province, Hangzhou, Zhejiang Province, China

3Bengbu Medical College, Bengbu, Anhui Province, China

4State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang Province, China

*These authors have contributed equally to this work

Correspondence to:

Xiao Chen, email: [email protected]

Keywords: Physapubescin B, STAT3, taxol resistance, ovarian cancer

Received: February 10, 2017     Accepted: June 28, 2017     Published: July 26, 2017

ABSTRACT

Ovarian cancer is the most lethal gynaecological malignancy. Recurrence and subsequent resistance to chemotherapy have become major obstacles to treating these diseases. In the present study, we showed that a natural withanolide isolated from the plant Physalis pubescens L. (Solanaceae), Physapubescin B, exhibited potent anti-tumor activity against ovarian cancer cells. Physapubescin B promoted apoptosis, induced cell-cycle arrest and inhibited invasion of ES-2 and A2780 cells. Physapubescin B treatment also resulted in suppression of the transcriptional activity of STAT3, an oncogenic transcription factor activated in many human malignancies including ovarian cancer, through disturbing the dimerization of STAT3, and thereby inhibited the nuclear translocation of Tyr705/Ser727-phosphorylated STAT3. The IL-6-stimulated activation of STAT3 and its downstream genes Cyclin D1, survivin, and Bcl-xL was also repressed by Physapubescin B. Furthermore, Physapubescin B sensitizes A2780 cells to taxol-induced cell growth inhibition in vitro. These findings strongly suggest that Physapubescin B has potential antitumor activity and may circumvent taxol resistance in human ovarian cancer cells through inhibition of aberrant activation of STAT3.


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