The novel JNK inhibitor AS602801 inhibits cancer stem cells in vitro and in vivo.
The novel JNK inhibitor AS602801 inhibits cancer stem cells in vitro and in vivo.
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DOI：
10.18632/oncotarget.8395
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发表时间：
2016-05-10
期刊：
影响因子：
--
通讯作者：
Kitanaka C
中科院分区：
文献类型：
--
作者：
Okada M;Kuramoto K;Takeda H;Watarai H;Sakaki H;Seino S;Seino M;Suzuki S;Kitanaka C
调查新开发的JNK抑制剂AS602801治疗炎症性子宫内膜异位症的有效性和安全性的第二阶段临床试验已经完成。我们现在正在研究AS602801在体外和体内是否对人类癌细胞起作用。在体外，AS602801对血清培养的非干细胞癌细胞以及来自人胰腺癌、非小细胞肺癌、卵巢癌和胶质母细胞瘤的癌症干细胞具有细胞毒性，其浓度不会降低正常人成纤维细胞的活力。AS602801还抑制了AS602801治疗后存活的癌症干细胞的自我更新和肿瘤启动能力。AS602801全身给药的剂量和时间不会对荷瘤小鼠的健康造成不利影响，从而减少了已建立的异种移植瘤中的癌症干细胞。这些发现表明AS602801是一种很有前途的抗癌干细胞制剂，似乎有必要进一步研究AS602801在癌症治疗中的作用。
A phase 2 clinical trial investigating the efficacy and safety of AS602801, a newly developed JNK inhibitor, in the treatment of inflammatory endometriosis is complete. We are now examining whether AS602801 acts against human cancer cells in vitro and in vivo. In vitro, AS602801 exhibited cytotoxicity against both serum-cultured non-stem cancer cells and cancer stem cells derived from human pancreatic cancer, non-small cell lung cancer, ovarian cancer and glioblastoma at concentrations that did not decrease the viability of normal human fibroblasts. AS602801 also inhibited the self-renewal and tumor-initiating capacity of cancer stem cells surviving AS602801 treatment. Cancer stem cells in established xenograft tumors were reduced by systemic administration of AS602801 at a dose and schedule that did not adversely affect the health of the tumor-bearing mice. These findings suggest AS602801 is a promising anti-cancer stem cell agent, and further investigation of the utility of AS602801 in the treatment of cancer seems warranted.
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影响因子：
--
作者：
Suzuki S;Okada M;Shibuya K;Seino M;Sato A;Takeda H;Seino S;Yoshioka T;Kitanaka C
通讯作者：
Kitanaka C
影响因子：
5.2
作者：
Okada, Masashi;Sato, Atsushi;Kitanaka, Chifumi
通讯作者：
Kitanaka, Chifumi
影响因子：
5.4
作者：
Chappell, James;Dalton, Stephen
通讯作者：
Dalton, Stephen
DOI：
10.1016/j.bbapap.2009.11.002
发表时间：
2010-03-01
影响因子：
3.2
作者：
Bogoyevitch, Marie A.;Ngoei, Kevin R. W.;Ng, Dominic C. H.
通讯作者：
Ng, Dominic C. H.
影响因子：
13.6
作者：
Ma, Frank Y.;Flanc, Robert S.;Nikolic-Paterson, David J.
通讯作者：
Nikolic-Paterson, David J.