XJIPC OpenIR  > 省部共建新疆特有药用资源利用重点实验室
Next-generation proteasome inhibitor MLN9708 sensitizes breast cancer cells to doxorubicin-induced apoptosis
Wang, H (Wang, Hao); Yu, Y (Yu, Yang); Jiang, Z (Jiang, Zheng); Cao, WM (Cao, Wen-Ming); Wang, ZY (Wang, Zhenyu); Dou, J (Dou, Jun); Zhao, YL (Zhao, Yanling); Cui, YF (Cui, Yunfu); Zhang, H (Zhang, Hong)
2016
Source PublicationSCIENTIFIC REPORTS
ISSN2045-2322
Volume6Issue:5Pages:1-13
Abstract

Doxorubicin (Dox), one of the most effective chemotherapy drug for cancer treatment, is limited by its severe side effects and chemoresistance. Dox induces DNA damage and leads to significant proteomic changes in the cancer cells, which makes the ubiquitin-proteasome system a potential target to enhance the efficacy of Dox therapy. The unsuccessful clinical trials of proteasome inhibitor PS-341 (bortezomib) in solid tumors led to the invention of MLN9708 (ixazomib), an orally bioavailable next-generation proteasome inhibitor with improved pharmacokinetic and pharmacodynamic features. In this preclinical study, we used eight human breast cancer cell lines, which represent the major molecular subtypes of breast cancer, to validate the cytotoxic effects of MLN9708, alone and in combination with Dox. We found that MLN9708 had cytotoxic effects, induced autophagy and MKP-1 expression, and enhanced Dox-induced apoptosis in these cell lines. MLN9708 also enhanced Dox-induced JNK and p38 phosphorylation and inhibited Dox-induced I kappa B alpha degradation. Our in vitro results suggest that MLN9708 has antitumor effects in breast cancer and can sensitize breast cancer cells to Dox treatment. This promising combination may be an effective and feasible therapeutic option for treating breast cancer and warrants clinical validation.

DOI10.1038/srep26456
Indexed BySCI
WOS IDWOS:000376364100001
Citation statistics
Cited Times:15[WOS]   [WOS Record]     [Related Records in WOS]
Document Type期刊论文
Identifierhttp://ir.xjipc.cas.cn/handle/365002/4659
Collection省部共建新疆特有药用资源利用重点实验室
Affiliation1.Harbin Med Univ, Affiliated Hosp 2, Dept Hepatopancreatobiliary Surg, Harbin 150086, Heilongjiang, Peoples R China
2.Univ Texas MD Anderson Canc Ctr, Dept Pathol, Houston, TX 77030 USA
3.Harbin Med Univ, Med Genet Lab, Harbin 150081, Heilongjiang, Peoples R China
4.Chinese Acad Med Sci, Peking Union Med Coll, Canc Hosp, Dept Colorectal Surg, Beijing 100021, Peoples R China
5.Zhejiang Canc Hosp, Dept Med Oncol, Hangzhou 310022, Zhejiang, Peoples R China
6.Jilin Univ, Hosp 2, Dept Breast Surg, Changchun 130041, Jilin, Peoples R China
7.Chinese Acad Sci, Xinjiang Tech Inst Phys & Chem, Xinjiang Key Lab Plant Resources & Nat Prod Chem, Urumqi 830011, Xinjiang, Peoples R China
8.Univ Texas MD Anderson Canc Ctr, Dept Mol & Translat Pathol, Houston, TX 77030 USA
Recommended Citation
GB/T 7714
Wang, H ,Yu, Y ,Jiang, Z ,et al. Next-generation proteasome inhibitor MLN9708 sensitizes breast cancer cells to doxorubicin-induced apoptosis[J]. SCIENTIFIC REPORTS,2016,6(5):1-13.
APA Wang, H .,Yu, Y .,Jiang, Z .,Cao, WM .,Wang, ZY .,...&Zhang, H .(2016).Next-generation proteasome inhibitor MLN9708 sensitizes breast cancer cells to doxorubicin-induced apoptosis.SCIENTIFIC REPORTS,6(5),1-13.
MLA Wang, H ,et al."Next-generation proteasome inhibitor MLN9708 sensitizes breast cancer cells to doxorubicin-induced apoptosis".SCIENTIFIC REPORTS 6.5(2016):1-13.
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