Apatinib Suppresses Gastric Cancer Stem Cells Properties by Inhibiting the Sonic Hedgehog Pathway.
Apatinib Suppresses Gastric Cancer Stem Cells Properties by Inhibiting the Sonic Hedgehog Pathway.
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DOI：
10.3389/fcell.2021.679806
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发表时间：
2021
影响因子：
5.5
通讯作者：
Zhong C
中科院分区：
文献类型：
--
作者：
Cao W;Li Y;Sun H;Yang C;Zhu J;Xie C;Li X;Wu J;Geng S;Wang L;Sun L;Geng G;Han H;Zhong C
胃癌干细胞的存在标志着胃癌的发生。SHH信号通路在维持GCSC特性中起着重要作用。阿帕替尼已在中国获批用于晚期胃癌（GC）治疗。然而，阿帕替尼是否可以靶向GCSC并影响SHH通路仍不清楚。本研究旨在探讨阿帕替尼对胃癌的抗肿瘤作用的机制。球形成细胞中GCSC标志物的表达水平和CD 133+细胞的数量显著升高。阿帕替尼通过抑制肿瘤球形成和细胞增殖、抑制GCSC标志物表达和CD133+细胞数量以及诱导凋亡，有效抑制GCSC性状。阿帕替尼下调SHH通路的激活;而SHH通路的上调减弱了阿帕替尼对GCSC的抑制作用。此外，阿帕替尼治疗显著延迟了肿瘤生长，并抑制了异种移植模型中的GCSC特征。我们的数据表明，阿帕替尼通过抑制SHH通路在体外和体内对GCSC表现出抑制作用，从而为阿帕替尼在GCSC抑制和晚期胃癌治疗中的治疗应用提供了新的见解。
The presence of gastric cancer stem cells (GCSCs) marks the onset of gastric carcinoma. The sonic hedgehog (SHH) pathway plays a vital role in the maintenance of GCSC characteristics. Apatinib has been approved in China for advanced gastric cancer (GC) treatment. However, whether apatinib can target GCSCs and affect the SHH pathway remains unclear. The present study aimed to investigate the underlying mechanism of apatinib’s antitumor effects on GC. The expression levels of GCSC markers and number of CD133+ cells were significantly elevated in the sphere-forming cells. Apatinib effectively suppressed GCSC traits by inhibiting tumorsphere formation and cell proliferation, suppressing GCSC markers expression and CD133+ cell number, and inducing apoptosis. Apatinib downregulated the activation of the SHH pathway; while upregulation of the SHH pathway attenuated the inhibitory effects of apatinib on GCSCs. Moreover, apatinib treatment significantly delayed tumor growth and inhibited GCSC characteristics in the xenograft model. Our data suggested that apatinib exhibited inhibitory effects on GCSCs by suppressing SHH pathway both in vitro and in vivo, thus providing new insights into the therapeutic application of apatinib in GCSC suppression and advanced gastric cancer treatment.
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影响因子：
--
作者：
Akyala AI;Peppelenbosch MP
通讯作者：
Peppelenbosch MP
DOI：
10.1002/stem.1219
发表时间：
2012-11
期刊：
Stem cells (Dayton, Ohio)
影响因子：
--
作者：
Debeb BG;Lacerda L;Xu W;Larson R;Solley T;Atkinson R;Sulman EP;Ueno NT;Krishnamurthy S;Reuben JM;Buchholz TA;Woodward WA
通讯作者：
Woodward WA
影响因子：
64.8
作者：
KINZLER, KW;RUPPERT, JM;VOGELSTEIN, B
通讯作者：
VOGELSTEIN, B
影响因子：
4.4
作者：
Molina-Castro, Silvia;Pereira-Marques, Joana;Varon, Christine
通讯作者：
Varon, Christine
影响因子：
5.8
作者：
Chen, Xiaofeng;Qiu, Tianzhu;Gu, Yanhong
通讯作者：
Gu, Yanhong