Synergistic antitumour activity of sorafenib in combination with tetrandrine is mediated by reactive oxygen species (ROS)/Akt signaling.
Synergistic antitumour activity of sorafenib in combination with tetrandrine is mediated by reactive oxygen species (ROS)/Akt signaling.
复制标题
索拉非尼与粉防己碱联合使用的协同抗肿瘤活性是由活性氧 (ROS)/Akt 信号传导介导的。
DOI：
10.1038/bjc.2013.334
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发表时间：
2013-07-23
影响因子：
8.8
通讯作者：
Li W
中科院分区：
文献类型：
--
作者：
Wan J;Liu T;Mei L;Li J;Gong K;Yu C;Li W
Sorafenib是一种有效的Raf激酶和几种受体酪氨酸激酶抑制剂，已被批准用于晚期肾癌和肝癌的临床治疗。将索拉非尼与其他药物联合使用，不仅可以减少毒副作用，还可以预防对索拉非尼的原发性和获得性耐药，从而提高其抗肿瘤疗效。我们以前观察到粉防己碱在人肝细胞癌中表现出强大的抗肿瘤作用。在这项研究中，我们研究了索拉非尼与粉防己碱联合的协同抗肿瘤活性。这是一项由两部分组成的研究，包括索拉非尼与粉防己碱联合使用对癌细胞的体外作用，以及该药物联合使用对裸鼠肿瘤异种移植的体内抗肿瘤功效。联合治疗显示出良好的协同抗肿瘤效果，同时保留了非致瘤细胞。其潜在的分子机制可能主要是激活线粒体死亡途径，诱导肿瘤细胞caspase依赖性凋亡。细胞内活性氧（ROS）的积累和随后Akt的激活也可能参与了细胞凋亡的诱导。索拉非尼联合粉防己碱的抗肿瘤活性可能归因于通过ROS/Akt信号通路诱导内在凋亡通路。这一发现为扩大索拉非尼的临床应用提供了一种新的途径。
Sorafenib is a potent inhibitor against Raf kinase and several receptor tyrosine kinases that has been approved for the clinical treatment of advanced renal and liver cancer. Combining sorafenib with other agents has been shown to improve its antitumour efficacy by not only reducing the toxic side effects but also preventing primary and acquired resistance to sorafenib. We have previously observed that tetrandrine exhibits potent antitumour effects in human hepatocellular carcinoma. In this study, we investigated the synergistic antitumour activity of sorafenib in combination with tetrandrine. This was a two-part investigation that included the in vitro effects of sorafenib in combination with tetrandrine on cancer cells and the in vivo antitumour efficacy of this drug combination on tumour xenografts in nude mice. Combined treatment showed a good synergistic antitumour effect yet spared nontumourigenic cells. The potential molecular mechanism may be mainly that it activated mitochondrial death pathway and induced caspase-dependent apoptosis in the cancer cells. Accumulation of intracellular reactive oxygen species (ROS) and subsequent activation of Akt may also be involved in apoptosis induction. The antitumour activity of sorafenib plus tetrandrine may be attributed to the induction of the intrinsic apoptosis pathway through ROS/Akt signaling. This finding provides a novel approach that may broaden the clinical application of sorafenib.
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CS055 (Chidamide/HBI-8000) 是一种新型组蛋白脱乙酰酶抑制剂，可诱导人白血病细胞 G1 期阻滞、ROS 依赖性细胞凋亡和分化
影响因子：
4.1
作者：
Gong, Ke;Xie, Jia;Li, Wenhua
通讯作者：
Li, Wenhua
影响因子：
45.3
作者：
Matei, Daniela;Sill, Michael W.;Birrer, Michael J.
通讯作者：
Birrer, Michael J.
DOI：
10.1200/jco.2011.37.1021
发表时间：
2011-10-20
期刊：
Journal of clinical oncology : official journal of the American Society of Clinical Oncology
影响因子：
--
作者：
Pawlik TM;Reyes DK;Cosgrove D;Kamel IR;Bhagat N;Geschwind JF
通讯作者：
Geschwind JF
影响因子：
11.4
作者：
Huber, S.;Oelsner, M.;Ringshausen, I.
通讯作者：
Ringshausen, I.
影响因子：
11.2
作者：
Liu, Li;Cao, Yichen;Carter, Christopher
通讯作者：
Carter, Christopher