SC66 inhibits the proliferation and induces apoptosis of human bladder cancer cells by targeting the AKT/β-catenin pathway.
SC66 inhibits the proliferation and induces apoptosis of human bladder cancer cells by targeting the AKT/β-catenin pathway.
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SC66通过靶向AKT/β-catenin通路抑制人膀胱癌细胞增殖并诱导细胞凋亡
DOI：
10.1111/jcmm.17005
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发表时间：
2021-11
影响因子：
5.3
通讯作者：
Cheng F
中科院分区：
文献类型：
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作者：
Chen W;Zhao S;Yu W;Rao T;Ruan Y;Zhu S;Xia Y;Song H;Cheng F
膀胱癌（BC）是泌尿生殖道的主要疾病，化疗是目前常用的主要治疗方法之一。 SC66是一种新型变构AKT抑制剂，据报道在许多其他类型肿瘤的进展中发挥有效的抑制作用，但尚未有关于其在BC中作用的研究报道。在这项研究中，我们发现 SC66 显着抑制 T24 和 5637 细胞的增殖和 EMT 介导的迁移和侵袭。此外，实验证实SC66通过诱导细胞凋亡、影响细胞周期来实现抗肿瘤作用。荧光素酶检测证实 SC66 通过 AKT/β-catenin 信号通路发挥抗肿瘤作用，并且在添加 β-catenin 信号通路激活剂 CHIR-99021 后，这种抑制作用被逆转。此外，动物研究表明，与对照组相比，腹腔注射SC66的实验组T24肿瘤裸鼠的肿瘤重量和体积明显减小，且SC66联合顺铂对肿瘤具有更好的抑制作用。 Western blot分析和免疫组织化学染色证实SC66在体内抑制EMT过程并通过AKT/β-catenin信号通路诱导细胞凋亡。总之，我们的研究表明 SC66 通过 AKT/β-catenin 信号通路发挥显着的抗肿瘤作用，从而为 BC 提供新的潜在治疗方法。
Bladder cancer (BC) is a major disease of the genitourinary tract, and chemotherapy is one of the main treatments commonly used at present. SC66 is a new type of allosteric AKT inhibitor that is reported to play an effective inhibitory role in the progression of many other types of tumours, but there is no reported research on its role in BC. In this study, we found that SC66 significantly inhibited the proliferation and EMT‐mediated migration and invasion of T24 and 5637 cells. In addition, experiments confirmed that SC66 achieved its antitumour effect by inducing cell apoptosis and affecting the cell cycle. Luciferase assays confirmed that SC66 exerted an antitumour effect through the AKT/β‐catenin signalling pathway, and this inhibitory effect was reversed after the addition of the β‐catenin signalling pathway activator, CHIR‐99021. In addition, animal studies have shown that, compared with the control group, the experimental group with SC66 intraperitoneal injection showed significantly reduced the tumour weight and volume in nude mice with T24 tumours and that SC66 combined with cisplatin achieved better inhibition on tumours. Western blot analysis and immunohistochemistry staining confirmed that SC66 inhibited the EMT process in vivo and induced apoptosis through the AKT/β‐catenin signalling pathway. In conclusion, our study demonstrated that SC66 exerts a significant antitumour effect through the AKT/β‐catenin signalling pathway, thereby providing a new potential treatment for BC.
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影响因子：
--
作者：
Luo KW;Lung WY;Chun-Xie;Luo XL;Huang WR
通讯作者：
Huang WR
DOI：
10.1007/978-1-4614-0899-4_15
发表时间：
2012-01-01
期刊：
NOTCH SIGNALING IN EMBRYOLOGY AND CANCER
影响因子：
--
作者：
Dang, Thao P.
通讯作者：
Dang, Thao P.
影响因子：
158.5
作者：
Grossman, HB;Natale, RB;Crawford, ED
通讯作者：
Crawford, ED
DOI：
10.1073/pnas.1019062108
发表时间：
2011-04-19
影响因子：
11.1
作者：
Jo, Hakryul;Lo, Pang-Kuo;Luo, Hongbo R.
通讯作者：
Luo, Hongbo R.
影响因子：
9
作者：
通讯作者：
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