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Combination chemotherapy with Zyflamend reduced the acquired resistance of bladder cancer cells to cisplatin through inhibiting NF kappa B signaling pathway

文献类型：期刊论文

作者Xue, Yanshi6; Yang, Lin3; Li, Junzun2,5; Yan, Yilin1; Jiang, Qinghui4,8; Shen, Lan2,5; Yang, Shuai2,5; Shen, Bing1; Huang, Ruimin4,8; Yan, Jun2,5,7
刊名ONCOTARGETS AND THERAPY
出版日期2018
卷号11页码:4413-4429
关键词Zyflamend cisplatin bladder cancer NF kappa B acquired resistance
ISSN号1178-6930
DOI10.2147/OTT.S162255
文献子类Article
英文摘要Background: Cisplatin-based chemotherapy is mainstay treatment in urinary bladder cancer (UBC). However, tumor recurrence frequently occurs with the acquisition of cisplatin resistance. We explored the potential effect of a polyherbal preparation, Zyflamend, on UBC cells resistant to cisplatin treatment. Methods: To establish a cisplatin-resistant human bladder cancer cell line, T24 cells were cultured in increasing concentrations of cisplatin for more than 10 months. These cells (T24R) were then treated with different concentrations of Zyflamend, and both proliferation and activity of nuclear factor kappaB (NF kappa B) signaling pathway were examined. To test the synergistic effect between Zyflamend and cisplatin, we treated T24R cells either with Zyflamend or cisplatin alone, or in combination. Apoptotic effect was evaluated by Annexin V/propidium iodide double staining, and the levels of the proteins involved in cell cycle and anti-apoptosis were examined by Western blotting. Finally, mice with palpable xenograft were treated either with cisplatin and Zyllamend alone or in combination for 28 days before they were sacrificed for measuring the sizes and weights of the tumor tissues. In addition, proliferation and apoptosis markers were examined by immunohistochemistry. Results: Comparing to that in the parental T24 cells, NF kappa B is constitutively active in cisplatin-resistant T24R cells. Zyflamend is capable of inhibiting the growth of T24, T24R, as well as another UBC cell line J82 in a concentration-dependent manner. Mechanistically, Zyflamend suppresses NF kappa B-mediated cell proliferation, survival, and invasion/angiogenesis and induces apoptosis. In addition, Zyflamend significantly increased the sensitivity of T24R and J82 cells to cisplatin treatment and these findings were confirmed in T24R xenograft model with reduced proliferation index and decreased expression of RelA and its downstream target MMP9. Conclusion: Zyflamend is capable of counteracting bladder cancer resistance to cisplatin by repressing proliferation and inducing apoptosis through targeting NF kappa B signaling pathway.
WOS关键词PROSTATE-CANCER ; ANDROGEN RECEPTOR ; DOWN-REGULATION ; TUMOR-GROWTH ; EXPRESSION ; APOPTOSIS ; ACTIVATION ; PROTEIN ; CARCINOMA ; INVASION
资助项目National Natural Science Foundation of China[81372168] ; National Natural Science Foundation of China[81470116] ; National Natural Science Foundation of China[81672873] ; National Natural Science Foundation of China[81572519] ; Wu Jieping Medical Foundation[320.6750.16051] ; Fundamental Research Funds for the Central Universities[090314380004] ; One Hundred Talent Program of Chinese Academy of Sciences[00000000] ; Research Fund of Institutes for Drug Discovery and Development, Chinese Academy of Sciences[CASIMM0120164001] ; New Chapter Incorporated[00000000]
WOS研究方向Biotechnology & Applied Microbiology ; Oncology
语种英语
WOS记录号WOS:000440330100002
出版者DOVE MEDICAL PRESS LTD
源URL[http://119.78.100.183/handle/2S10ELR8/272304]  
专题分子影像中心（筹）
通讯作者Huang, Ruimin; Guo, Hongqian
作者单位1.Shanghai Jiao Tong Univ, Shanghai Gen Hosp, Dept Urol, Shanghai, Peoples R China;
2.Nanjing Univ, Model Anim Res Ctr, MOE Key Lab Model Anim Dis Study, Nanjing, Jiangsu, Peoples R China;
3.Nanjing Univ, Med Sch, Inst Urol, Dept Urol,Nanjing Drum Tower Hosp, Nanjing, Jiangsu, Peoples R China;
4.Univ Chinese Acad Sci, Beijing, Peoples R China;
5.Nanjing Univ, Model Anim Res Ctr, State Key Lab Pharmaceut Biotechnol, Nanjing, Jiangsu, Peoples R China;
6.Nanjing Med Univ, Clin Coll, Nanjing Drum Tower Hosp, Dept Urol, 321 Zhongshan Rd, Nanjing 210008, Jiangsu, Peoples R China;
7.Collaborat Innovat Ctr Genet & Dev, Shanghai, Peoples R China
8.Chinese Acad Sci, Shanghai Inst Mat Med, 555 Zuchongzhi Rd, Shanghai 201203, Peoples R China;
推荐引用方式
GB/T 7714		 Xue, Yanshi,Yang, Lin,Li, Junzun,et al. Combination chemotherapy with Zyflamend reduced the acquired resistance of bladder cancer cells to cisplatin through inhibiting NF kappa B signaling pathway[J]. ONCOTARGETS AND THERAPY,2018,11:4413-4429.
APA Xue, Yanshi.,Yang, Lin.,Li, Junzun.,Yan, Yilin.,Jiang, Qinghui.,...&Guo, Hongqian.(2018).Combination chemotherapy with Zyflamend reduced the acquired resistance of bladder cancer cells to cisplatin through inhibiting NF kappa B signaling pathway.ONCOTARGETS AND THERAPY,11,4413-4429.
MLA Xue, Yanshi,et al."Combination chemotherapy with Zyflamend reduced the acquired resistance of bladder cancer cells to cisplatin through inhibiting NF kappa B signaling pathway".ONCOTARGETS AND THERAPY 11(2018):4413-4429.

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来源：上海药物研究所

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