Huachansu suppresses human bladder cancer cell growth through the Fas/Fasl and TNF- alpha/TNFR1 pathway in vitro and in vivo.
Huachansu suppresses human bladder cancer cell growth through the Fas/Fasl and TNF- alpha/TNFR1 pathway in vitro and in vivo.
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Huachansu通过FAS/FASL和TNF-Alpha/TNFR1途径在体外和体内抑制人膀胱癌细胞的生长。
DOI：
10.1186/s13046-015-0134-9
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发表时间：
2015-02-25
期刊：
影响因子：
--
通讯作者：
Ye Z
中科院分区：
文献类型：
--
作者：
Yang T;Shi R;Chang L;Tang K;Chen K;Yu G;Tian Y;Guo Y;He W;Song X;Xu H;Ye Z
华蟾素（HCS）是从蟾蜍毒中提取的一类毒性甾体化合物，是一种有价值的抗肿瘤药物。然而，HCS对膀胱癌的作用尚未阐明。本研究旨在探讨HCS对膀胱癌的体内外抗肿瘤作用及其相关机制。MTS法检测HCS作用后T24、EJ、RT-4、SV-HUC-1细胞的存活率，透射电镜观察细胞形态学变化。流式细胞仪检测HCS诱导的早期细胞凋亡，Western blot检测凋亡相关分子Bax、Bcl-2、XIAP、PARP、cleaved-Caspases 3、8、9的表达水平。观察HCS对Fas/FasL、TNF-α/TNFR 1表达的影响，以及对NF-κ B B通路的激活，并进一步探讨这些通路在HCS诱导细胞凋亡中的作用。最后，采用裸鼠移植瘤模型进一步研究HCS的体内抗肿瘤作用。结果表明，HCS能有效地抑制人膀胱癌细胞株的增殖并诱导其凋亡。HCS处理后Fas、FasL、TNF-α在mRNA和蛋白水平均升高。此外，下调TNF-α、TNFR 1、Fas或抑制Fas/FasL相互作用可减少HCS诱导的死亡细胞的相对数量。在体内，HCS治疗显着抑制肿瘤生长和诱导细胞凋亡的裸鼠移植瘤。HCS在体内外均能有效抑制人膀胱癌细胞的增殖并诱导其凋亡，其作用主要通过Fas/FasL和TNF-α/TNFR 1途径介导。本文的在线版本（doi：10.1186/s13046-015-0134-9）包含补充材料，可供授权用户使用。
Huachansu (HCS), a class of toxic steroids extracted from toad venom, which has been shown to be a valuable anticancer drug in many kinds of cancers. However, the effect of HCS on bladder cancer has not been elucidated. In this study, we focused on the antitumor activities and related mechanisms of HCS on bladder cancer in vitro and in vivo. Cell viability of T24, EJ, RT-4, SV-HUC-1 cells after HCS treatment was measured by MTS, whereas the changes of cell morphology were observed by transmission electron microscopy. The early apoptosis induced by HCS was evaluated by flow cytometry, and the expression level of apoptosis-related molecules (Bax, Bcl-2, XIAP, PARP, cleaved-Caspases 3, 8, 9) was detected using Western blot. We then evaluated the impact of HCS on the expression of Fas/Fasl, TNF- alpha/TNFR1, and the activation of NF-Kappa B pathway, and furthermore the effect of these pathways in HCS induced-apoptosis were also detected. At last, xenograft tumor in nude mice was used to further investigate the antitumor effect of HCS in vivo. Our results showed that HCS could efficiently inhibit proliferation and induce apoptosis in human bladder cancer cell lines. The expression of Fas, Fasl, TNF- alpha were all elevated at both mRNA and protein level after HCS treatment. Furthermore, down regulation of TNF- alpha, TNFR1, Fas or inhibition of Fas/Fasl interaction decreased the relative number of death cells induced by HCS. In vivo, HCS treatment significantly suppressed tumor growth and induced apoptosis in xenografts tumor in nude mice. HCS could efficiently inhibit proliferation and induce apoptosis in human bladder cancer cells in vitro and in vivo, which is largely mediated by Fas/Fasl and TNF- alpha/TNFR1 pathway. The online version of this article (doi:10.1186/s13046-015-0134-9) contains supplementary material, which is available to authorized users.
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影响因子：
6.2
作者：
Meng, Zhiqiang;Yang, Peiying;Shen, Yehua;Bei, Wenying;Zhang, Ying;Ge, Yongqian;Newman, Robert A.;Cohen, Lorenzo;Liu, Luming;Thornton, Bob;Chang, David Z.;Liao, Zongxing;Kurzrock, Razelle
通讯作者：
Kurzrock, Razelle
影响因子：
64.5
作者：
Micheau, O;Tschopp, J
通讯作者：
Tschopp, J
影响因子：
2.1
作者：
Gros, L;Reyne, G;Meunier, G
通讯作者：
Meunier, G
影响因子：
3.4
作者：
Chen, K. T.;Chou, C. H.;Liu, Y. H.
通讯作者：
Liu, Y. H.
癌症战争：天然产品的反击。
影响因子：
5.5
作者：
Basmadjian C;Zhao Q;Bentouhami E;Djehal A;Nebigil CG;Johnson RA;Serova M;de Gramont A;Faivre S;Raymond E;Désaubry LG
通讯作者：
Désaubry LG