Drug Resistance Associates With Activation of Nrf2 in MCF-7/DOX Cells, and Wogonin Reverses it by Down-Regulating Nrf2-Mediated Cellular Defense Response
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作者:
Zhong, Yan
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China Pharmaceut Univ, State Key Lab Nat Med, Nanjing 210009, Jiangsu, Peoples R ChinaChina Pharmaceut Univ, State Key Lab Nat Med, Nanjing 210009, Jiangsu, Peoples R China
Zhong, Yan
[1
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Zhang, Fengyi
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China Pharmaceut Univ, State Key Lab Nat Med, Nanjing 210009, Jiangsu, Peoples R ChinaChina Pharmaceut Univ, State Key Lab Nat Med, Nanjing 210009, Jiangsu, Peoples R China
Zhang, Fengyi
[1
]
Sun, Zhongying
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China Pharmaceut Univ, State Key Lab Nat Med, Nanjing 210009, Jiangsu, Peoples R ChinaChina Pharmaceut Univ, State Key Lab Nat Med, Nanjing 210009, Jiangsu, Peoples R China
Sun, Zhongying
[1
]
Zhou, Wei
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China Pharmaceut Univ, State Key Lab Nat Med, Nanjing 210009, Jiangsu, Peoples R ChinaChina Pharmaceut Univ, State Key Lab Nat Med, Nanjing 210009, Jiangsu, Peoples R China
Zhou, Wei
[1
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Li, Zhi-Yu
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China Pharmaceut Univ, Dept Med Chem, Nanjing 210009, Jiangsu, Peoples R ChinaChina Pharmaceut Univ, State Key Lab Nat Med, Nanjing 210009, Jiangsu, Peoples R China
Li, Zhi-Yu
[2
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You, Qi-Dong
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China Pharmaceut Univ, Dept Med Chem, Nanjing 210009, Jiangsu, Peoples R ChinaChina Pharmaceut Univ, State Key Lab Nat Med, Nanjing 210009, Jiangsu, Peoples R China
You, Qi-Dong
[2
]
Guo, Qing-Long
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China Pharmaceut Univ, State Key Lab Nat Med, Nanjing 210009, Jiangsu, Peoples R ChinaChina Pharmaceut Univ, State Key Lab Nat Med, Nanjing 210009, Jiangsu, Peoples R China
Guo, Qing-Long
[1
]
Hu, Rong
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China Pharmaceut Univ, State Key Lab Nat Med, Nanjing 210009, Jiangsu, Peoples R ChinaChina Pharmaceut Univ, State Key Lab Nat Med, Nanjing 210009, Jiangsu, Peoples R China
Hu, Rong
[1
]
机构:
[1] China Pharmaceut Univ, State Key Lab Nat Med, Nanjing 210009, Jiangsu, Peoples R China
[2] China Pharmaceut Univ, Dept Med Chem, Nanjing 210009, Jiangsu, Peoples R China
Acquired resistance to doxorubicin (DOX) is a serious therapeutic problem in breast cancer patients. In this study, we investigated whether nuclear factor erythroid 2-related factor 2 (Nrf2) was associated with drug resistant in DOX resistant MCF-7 (MCF-7/DOX) cells, and if wogonin, a flavonoid isolated from the root of Scutellaria baicalensis Georgi, could reverse drug resistance in MCF-7/DOX cells. We found that the endogenous expression of Nrf2 as well as its target proteins heme oxygenase-1 (HO-1), NADP(H):quinone oxidoreductase (NQO) in MCF-7/DOX cells was higher than that in MCF-7 cells. Tert-butylhydroquinone treatment increased the expression Nrf2, HO-1, and NQO-1, and enhanced resistance of MCF-7 cells to DOX. Similarly, intracellular Nrf2 protein level was significantly decreased in MCF-7/DOX cells and DOX resistance was partially reversed by Nrf2 siRNA. Wogonin downregulated the Nrf2-dependent response and partly reversed DOX resistance in MCF-7/DOX cells. These results suggested that activation of Nrf2 was associated with drug resistance in MCF-7/DOX cells. Wogonin reversed drug resistance and its reversal mechanism might be due to the suppression of Nrf2 signaling pathway, indicating the feasibility of using Nrf2 inhibitors to increase efficacy of chemotherapeutic drugs. (c) 2012 Wiley Periodicals, Inc.
机构:
Sun Yat Sen Univ, Sch Pharmaceut Sci, Guangzhou 510006, Guangdong, Peoples R ChinaSun Yat Sen Univ, Sch Pharmaceut Sci, Guangzhou 510006, Guangdong, Peoples R China
Xia, Chen
Bai, Xupeng
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Sun Yat Sen Univ, Sch Pharmaceut Sci, Guangzhou 510006, Guangdong, Peoples R ChinaSun Yat Sen Univ, Sch Pharmaceut Sci, Guangzhou 510006, Guangdong, Peoples R China
Bai, Xupeng
Hou, Xiangyu
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Sun Yat Sen Univ, Sch Pharmaceut Sci, Guangzhou 510006, Guangdong, Peoples R ChinaSun Yat Sen Univ, Sch Pharmaceut Sci, Guangzhou 510006, Guangdong, Peoples R China
Hou, Xiangyu
Gou, Xiaoli
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Sun Yat Sen Univ, Sch Pharmaceut Sci, Guangzhou 510006, Guangdong, Peoples R ChinaSun Yat Sen Univ, Sch Pharmaceut Sci, Guangzhou 510006, Guangdong, Peoples R China
Gou, Xiaoli
Wang, Yongtao
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Sun Yat Sen Univ, Sch Pharmaceut Sci, Guangzhou 510006, Guangdong, Peoples R ChinaSun Yat Sen Univ, Sch Pharmaceut Sci, Guangzhou 510006, Guangdong, Peoples R China
Wang, Yongtao
Zeng, Hang
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Sun Yat Sen Univ, Sch Pharmaceut Sci, Guangzhou 510006, Guangdong, Peoples R ChinaSun Yat Sen Univ, Sch Pharmaceut Sci, Guangzhou 510006, Guangdong, Peoples R China
Zeng, Hang
Huang, Min
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Sun Yat Sen Univ, Sch Pharmaceut Sci, Guangzhou 510006, Guangdong, Peoples R ChinaSun Yat Sen Univ, Sch Pharmaceut Sci, Guangzhou 510006, Guangdong, Peoples R China
Huang, Min
Jin, Jing
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Sun Yat Sen Univ, Sch Pharmaceut Sci, Guangzhou 510006, Guangdong, Peoples R ChinaSun Yat Sen Univ, Sch Pharmaceut Sci, Guangzhou 510006, Guangdong, Peoples R China
机构:
Guangzhou Univ Chinese Med, Guangdong Prov Acad Chinese Med Sci, State Key Lab Dampness Syndrome Chinese Med, Affiliated Hosp 2, Guangzhou, Peoples R ChinaGuangzhou Univ Chinese Med, Guangdong Prov Acad Chinese Med Sci, State Key Lab Dampness Syndrome Chinese Med, Affiliated Hosp 2, Guangzhou, Peoples R China
Xie, Ying
Feng, Sen-ling
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Guangzhou Med Univ, Dept Pharm, Key Lab Major Obstet Dis Guangdong Prov, Affiliated Hosp 3, Guangzhou, Peoples R ChinaGuangzhou Univ Chinese Med, Guangdong Prov Acad Chinese Med Sci, State Key Lab Dampness Syndrome Chinese Med, Affiliated Hosp 2, Guangzhou, Peoples R China
Feng, Sen-ling
He, Fang
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Macau Univ Sci & Technol, State Key Lab Qual Res Chinese Med, Macau, Peoples R ChinaGuangzhou Univ Chinese Med, Guangdong Prov Acad Chinese Med Sci, State Key Lab Dampness Syndrome Chinese Med, Affiliated Hosp 2, Guangzhou, Peoples R China
He, Fang
Yan, Pei-Yu
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Macau Univ Sci & Technol, State Key Lab Qual Res Chinese Med, Macau, Peoples R ChinaGuangzhou Univ Chinese Med, Guangdong Prov Acad Chinese Med Sci, State Key Lab Dampness Syndrome Chinese Med, Affiliated Hosp 2, Guangzhou, Peoples R China
Yan, Pei-Yu
Yao, Xiao-Jun
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Macau Univ Sci & Technol, State Key Lab Qual Res Chinese Med, Macau, Peoples R ChinaGuangzhou Univ Chinese Med, Guangdong Prov Acad Chinese Med Sci, State Key Lab Dampness Syndrome Chinese Med, Affiliated Hosp 2, Guangzhou, Peoples R China
Yao, Xiao-Jun
Fan, Xing-Xing
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Macau Univ Sci & Technol, State Key Lab Qual Res Chinese Med, Macau, Peoples R ChinaGuangzhou Univ Chinese Med, Guangdong Prov Acad Chinese Med Sci, State Key Lab Dampness Syndrome Chinese Med, Affiliated Hosp 2, Guangzhou, Peoples R China
Fan, Xing-Xing
Leung, Elaine Lai-Han
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Univ Macau, Fac Hlth Sci, Macau, Peoples R ChinaGuangzhou Univ Chinese Med, Guangdong Prov Acad Chinese Med Sci, State Key Lab Dampness Syndrome Chinese Med, Affiliated Hosp 2, Guangzhou, Peoples R China
Leung, Elaine Lai-Han
Zhou, Hua
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Guangzhou Univ Chinese Med, Guangdong Prov Acad Chinese Med Sci, State Key Lab Dampness Syndrome Chinese Med, Affiliated Hosp 2, Guangzhou, Peoples R ChinaGuangzhou Univ Chinese Med, Guangdong Prov Acad Chinese Med Sci, State Key Lab Dampness Syndrome Chinese Med, Affiliated Hosp 2, Guangzhou, Peoples R China
机构:
Federal Research Center for Fundamental and Translational Medicine, NovosibirskFederal Research Center for Fundamental and Translational Medicine, Novosibirsk
Menshchikova E.B.
Chechushkov A.V.
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Federal Research Center for Fundamental and Translational Medicine, NovosibirskFederal Research Center for Fundamental and Translational Medicine, Novosibirsk
Chechushkov A.V.
Kozhin P.M.
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Federal Research Center for Fundamental and Translational Medicine, NovosibirskFederal Research Center for Fundamental and Translational Medicine, Novosibirsk
Kozhin P.M.
Kholshin S.V.
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Novosibirsk State Pedagogical University, NovosibirskFederal Research Center for Fundamental and Translational Medicine, Novosibirsk
Kholshin S.V.
Kandalintseva N.V.
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Novosibirsk State Pedagogical University, NovosibirskFederal Research Center for Fundamental and Translational Medicine, Novosibirsk
Kandalintseva N.V.
Martinovich G.G.
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Belarusian State University, MinskFederal Research Center for Fundamental and Translational Medicine, Novosibirsk
Martinovich G.G.
Zenkov N.K.
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Federal Research Center for Fundamental and Translational Medicine, NovosibirskFederal Research Center for Fundamental and Translational Medicine, Novosibirsk
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Shandong Univ Tradit Chinese Med, Clin Coll 1, Jinan 250014, Shandong, Peoples R China
Shandong First Med Univ, Breast Canc Ctr, Shandong Canc Hosp & Inst, Shandong Acad Med Sci, Jinan 250117, Shandong, Peoples R ChinaShandong Univ Tradit Chinese Med, Clin Coll 1, Jinan 250014, Shandong, Peoples R China
Shao, Wenna
Wang, Xinzhao
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Shandong First Med Univ, Breast Canc Ctr, Shandong Canc Hosp & Inst, Shandong Acad Med Sci, Jinan 250117, Shandong, Peoples R China
RemeGen Ltd, 58 Middle Beijing Rd, Yantai 264006, Shandong, Peoples R ChinaShandong Univ Tradit Chinese Med, Clin Coll 1, Jinan 250014, Shandong, Peoples R China
Wang, Xinzhao
Liu, Zhaoyun
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Shandong First Med Univ, Breast Canc Ctr, Shandong Canc Hosp & Inst, Shandong Acad Med Sci, Jinan 250117, Shandong, Peoples R ChinaShandong Univ Tradit Chinese Med, Clin Coll 1, Jinan 250014, Shandong, Peoples R China
Liu, Zhaoyun
Song, Xiang
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Shandong Univ Tradit Chinese Med, Clin Coll 1, Jinan 250014, Shandong, Peoples R China
Shandong First Med Univ, Breast Canc Ctr, Shandong Canc Hosp & Inst, Shandong Acad Med Sci, Jinan 250117, Shandong, Peoples R ChinaShandong Univ Tradit Chinese Med, Clin Coll 1, Jinan 250014, Shandong, Peoples R China
Song, Xiang
Wang, Fukai
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Shandong First Med Univ, Breast Canc Ctr, Shandong Canc Hosp & Inst, Shandong Acad Med Sci, Jinan 250117, Shandong, Peoples R ChinaShandong Univ Tradit Chinese Med, Clin Coll 1, Jinan 250014, Shandong, Peoples R China
Wang, Fukai
Liu, Xiaoyu
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Shandong Univ Tradit Chinese Med, Clin Coll 1, Jinan 250014, Shandong, Peoples R China
Shandong First Med Univ, Breast Canc Ctr, Shandong Canc Hosp & Inst, Shandong Acad Med Sci, Jinan 250117, Shandong, Peoples R ChinaShandong Univ Tradit Chinese Med, Clin Coll 1, Jinan 250014, Shandong, Peoples R China
Liu, Xiaoyu
Yu, Zhiyong
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Shandong Univ Tradit Chinese Med, Clin Coll 1, Jinan 250014, Shandong, Peoples R China
Shandong First Med Univ, Breast Canc Ctr, Shandong Canc Hosp & Inst, Shandong Acad Med Sci, Jinan 250117, Shandong, Peoples R ChinaShandong Univ Tradit Chinese Med, Clin Coll 1, Jinan 250014, Shandong, Peoples R China