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Journal of Oncology
Volume 2019, Article ID 2024648, 14 pages
https://doi.org/10.1155/2019/2024648
Research Article

Dovitinib Triggers Apoptosis and Autophagic Cell Death by Targeting SHP-1/p-STAT3 Signaling in Human Breast Cancers

1Department of Nursing, St. Mary’s Junior College of Medicine, Nursing and Management, Yilan 26647, Taiwan
2Institute of Long-Term Care, Mackay Medical College, New Taipei City 25245, Taiwan
3Department of Veterinary Medicine, School of Veterinary Medicine, National Taiwan University, 1 Sec 4 Roosevelt Road, Taipei 10617, Taiwan
4Holistic Education Center, Mackay Medical College, New Taipei City 25245, Taiwan
5Animal Cancer Center, College of Bioresources and Agriculture, National Taiwan University, 1 Sec 4 Roosevelt Road, Taipei 10617, Taiwan

Correspondence should be addressed to Chen-Si Lin; wt.ude.utn@001nilsc

Received 29 June 2019; Accepted 29 July 2019; Published 14 August 2019

Guest Editor: Chia-Jung Li

Copyright © 2019 Yi-Han Chiu et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Breast cancer is the most common cancer and the leading cause of cancer deaths in women worldwide. The rising incidence rate and female mortality make it a significant public health concern in recent years. Dovitinib is a novel multitarget receptor tyrosine kinase inhibitor, which has been enrolled in several clinical trials in different cancers. However, its antitumor efficacy has not been well determined in breast cancers. Our results demonstrated that dovitinib showed significant antitumor activity in human breast cancer cell lines with dose- and time-dependent manners. Downregulation of phosphor-(p)-STAT3 and its subsequent effectors Mcl-1 and cyclin D1 was responsible for this drug effect. Ectopic expression of STAT3 rescued the breast cancer cells from cell apoptosis induced by dovitinib. Moreover, SHP-1 inhibitor reversed the downregulation of p-STAT3 induced by dovitinib, indicating that SHP-1 mediated the STAT3 inhibition effect of dovitinib. In addition to apoptosis, we found for the first time that dovitinib also activated autophagy to promote cell death in breast cancer cells. In conclusion, dovitinib induced both apoptosis and autophagy to block the growth of breast cancer cells by regulating the SHP-1-dependent STAT3 inhibition.