Next-generation proteasome inhibitor oprozomib enhances sensitivity to doxorubicin in triple-negative breast cancer cells

被引:0
作者
Shi, Yonghua [1 ]
Bieerkehazhi, Shayahati [2 ]
Ma, Hong [1 ]
机构
[1] Xinjiang Med Univ, Basic Med Coll, Dept Pathol, Urumqi 830011, Xinjiang, Peoples R China
[2] Xinjiang Med Univ, Coll Publ Hlth, Urumqi 830011, Xinjiang, Peoples R China
来源
INTERNATIONAL JOURNAL OF CLINICAL AND EXPERIMENTAL PATHOLOGY | 2018年 / 11卷 / 05期
关键词
Proteasome inhibitor; oprozomib; doxorubicin; drug resistance; breast cancer; NF-KAPPA-B; SOLID TUMORS; ACTIVATION; BORTEZOMIB; SYSTEM; CARFILZOMIB; CARCINOMA; SURVIVAL; HEAD;
D O I
暂无
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Doxorubicin (DOX) is the most common chemotherapeutic drug for treatment of breast cancer but intrinsic and acquired resistance frequently occurs and severe side effects occur at high doses. DOX might induce activation of NF-kappa B causing this resistance, in which case proteasome inhibitors could inhibit activation of NF-kappa B by blocking inhibitory factor KB-alpha degradation. Triple-negative breast cancer (TNBC) is highly progressive and there are no established therapeutic targets against TNBC. Although some proteasome inhibitors have been shown to have antitumor effects in breast cancer, the effect of orally bioavailable proteasome inhibitor oprozomib on TNBC proliferation remains unclear. In the present study, we investigated the role of oprozomib in two TNBC lines, MDA-MB-231 and BT-549. Oprozomib had cytotoxic effects on TNBC cells and increased DOX-induced cytotoxic effects and apoptosis by enhancing DOX-induced JNK/p38 MAPK phosphorylation and inhibiting DOX-induced inhibitory factor eB alpha degradation. These results suggest that oprozomib has potent antitumor effects on TNBC in vitro and can sensitize TNBC cells to DOX treatment. The combination of DOX and oprozomib may be an effective and feasible therapeutic option for TNBC.
引用
收藏
页码:2347 / 2355
页数:9
相关论文
共 43 条
[1]   Subtyping of Triple-Negative Breast Cancer: Implications for Therapy [J].
Abramson, Vandana G. ;
Lehmann, Brian D. ;
Ballinger, Tarah J. ;
Pietenpol, Jennifer A. .
CANCER, 2015, 121 (01) :8-16
[2]   Ubiquitin-like protein conjugation and the ubiquitin-proteasome system as drug targets [J].
Bedford, Lynn ;
Lowe, James ;
Dick, Lawrence R. ;
Mayer, R. John ;
Brownell, James E. .
NATURE REVIEWS DRUG DISCOVERY, 2011, 10 (01) :29-46
[3]   High IKK expression is associated with reduced time to recurrence and cancer specific survival in oestrogen receptor (ER)-positive breast cancer [J].
Bennett, Lindsay ;
Quinn, Jean ;
McCall, Pamela ;
Mallon, Elizabeth A. ;
Horgan, Paul G. ;
McMillan, Donald C. ;
Paul, Andrew ;
Edwards, Joanne .
INTERNATIONAL JOURNAL OF CANCER, 2017, 140 (07) :1633-1644
[4]  
Bian DH, 2017, AM J CANCER RES, V7, P28
[5]   Novel Src/ Abl tyrosine kinase inhibitor bosutinib suppresses neuroblastoma growth via inhibiting Src/ Abl signaling [J].
Bieerkehazhi, Shayahati ;
Chen, Zhenghu ;
Zhao, Yanling ;
Yu, Yang ;
Zhang, Huiyuan ;
Vasudevan, Sanjeev A. ;
Woodfield, Sarah E. ;
Tao, Ling ;
Yi, Joanna S. ;
Muscal, Jodi A. ;
Pang, Jonathan C. ;
Guan, Shan ;
Zhang, Hong ;
Nuchtern, Jed G. ;
Li, Hui ;
Li, Huiwu ;
Yang, Jianhua .
ONCOTARGET, 2017, 8 (01) :1469-1480
[6]   Approval summary for bortezomib for injection in the treatment of multiple myeloma [J].
Bross, PF ;
Kane, R ;
Farrell, AT ;
Abraham, S ;
Benson, K ;
Brower, ME ;
Bradley, S ;
Gobburu, JV ;
Goheer, A ;
Lee, SL ;
Leighton, J ;
Liang, CY ;
Lostritto, RT ;
McGuinn, WD ;
Morse, DE ;
Rahman, A ;
Rosario, LA ;
Verbois, SL ;
Williams, G ;
Wang, YC ;
Pazdur, R .
CLINICAL CANCER RESEARCH, 2004, 10 (12) :3954-3964
[7]   Sensitization of U937 leukemia cells to doxorubicin by the MG132 proteasome inhibitor induces an increase in apoptosis by suppressing NF-kappa B and mitochondrial membrane potential loss [J].
Cesar Ortiz-Lazareno, Pablo ;
Bravo-Cuellar, Alejandro ;
Manuel Lerma-Diaz, Jose ;
Felipe Jave-Suarez, Luis ;
Aguilar-Lemarroy, Adriana ;
Ramiro Dominguez-Rodriguez, Jorge ;
Gonzalez-Ramella, Oscar ;
De Cellis, Ruth ;
Gomez-Lomeli, Paulina ;
Hernandez-Flores, Georgina .
CANCER CELL INTERNATIONAL, 2014, 14
[8]   Triple-negative breast cancer: treatment challenges and solutions [J].
Collignon, Joelle ;
Lousberg, Laurence ;
Schroeder, Helene ;
Jerusalem, Guy .
BREAST CANCER-TARGETS AND THERAPY, 2016, 8 :93-107
[9]   P-Glycoprotein Inhibition Sensitizes Human Breast Cancer Cells to Proteasome Inhibitors [J].
Deshmukh, Rahul R. ;
Kim, Seongho ;
Elghoul, Yasmine ;
Dou, Q. Ping .
JOURNAL OF CELLULAR BIOCHEMISTRY, 2017, 118 (05) :1239-1248
[10]   Doxorubicin induces atypical NF-κB activation through c-Abl kinase activity in breast cancer cells [J].
Esparza-Lopez, Jose ;
Medina-Franco, Heriberto ;
Escobar-Arriaga, Elizabeth ;
Leon-Rodriguez, Eucario ;
Zentella-Dehesa, Alejandro ;
Ibarra-Sanchez, Maria J. .
JOURNAL OF CANCER RESEARCH AND CLINICAL ONCOLOGY, 2013, 139 (10) :1625-1635