Klotho sensitizes human lung cancer cell line to cisplatin via PI3k/Akt pathway.
Klotho sensitizes human lung cancer cell line to cisplatin via PI3k/Akt pathway.
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Klotho 通过 PI3k/Akt 途径使人肺癌细胞系对顺铂敏感
DOI：
10.1371/journal.pone.0057391
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Wu J
中科院分区：
文献类型：
--
作者：
Wang Y;Chen L;Huang G;He D;He J;Xu W;Zou C;Zong F;Li Y;Chen B;Wu S;Zhao W;Wu J
Klotho于1997年首次被发现，并被认为是一种抗衰老基因。越来越多的证据表明klotho通过抑制癌细胞的增殖和促进癌细胞的凋亡而与包括肺癌、乳腺癌等在内的癌症有着密切的关系。顺铂是目前一线化疗中应用最广泛的药物。然而，顺铂耐药癌细胞的增加已成为癌症临床管理的主要障碍。在我们的研究中，我们首次证明了klotho可以减弱肺癌对顺铂化疗的耐药性，并且klotho过表达的耐药细胞的凋亡显著增加。然而，klotho基因敲减的细胞显示出对化疗的抗性增强。进一步的分析表明，用特异性抑制剂（LY 294002）抑制PI 3 K/Akt通路减弱了干扰klotho shRNA后对肿瘤生长的促进作用。此外，我们证明了klotho在异种移植裸鼠模型中调节对顺铂的耐药性。这些结果表明，klotho可以提高肺癌细胞对化疗的耐药性，并可能作为一个潜在的靶点，肺癌耐顺铂化疗的基因治疗。
Klotho was first identified in 1997 and has been considered as an anti-aging gene. Emerging evidence demonstrates that klotho has a close relationship with cancers, including lung cancer, breast cancer, etc, by inhibiting the proliferation and promoting apoptosis of cancer cells. Cisplatin has been the most widely used drug in the first-line chemotherapy. However, the increase in cisplatin-resistant cancer cells has become a major obstacle in clinical management of cancers. In our study, we for the first time demonstrated that klotho could attenuate the resistance of lung cancer to cisplatin based chemotherapy and the apoptosis of the resistant cells with klotho overexpression was markedly increased. However, klotho knockdown cells showed enhanced resistance to chemotherapy. Further analysis showed that inhibition of PI3K/Akt pathway with specific inhibitor (LY294002) attenuated the promotive effects on cancer growth following interfering with klotho shRNA. Moreover, we demonstrated that klotho modulated the resistance to cisplatin in a xenograft nude mice model. These observations suggested that klotho could improve the resistance of lung cancer cells to chemotherapy and may serve as a potential target for the gene therapy of lung cancers resistant to cisplatin based chemotherapy.
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影响因子：
9.7
作者：
Shibata, Tatsuhiro;Kokubu, Akiko;Hirohashi, Setsuo
通讯作者：
Hirohashi, Setsuo
影响因子：
11.5
作者：
Abramovitz, Lilach;Rubinek, Tamar;Wolf, Ido
通讯作者：
Wolf, Ido
Klotho 抑制人肺癌细胞系 A549 生长并促进细胞凋亡
DOI：
10.1186/1756-9966-29-99
发表时间：
2010-07-19
期刊：
Journal of experimental & clinical cancer research : CR
影响因子：
--
作者：
Chen B;Wang X;Zhao W;Wu J
通讯作者：
Wu J
影响因子：
--
作者：
Hart JR;Vogt PK
通讯作者：
Vogt PK
DOI：
10.1016/j.jconrel.2011.03.032
发表时间：
2011-10-30
期刊：
Journal of controlled release : official journal of the Controlled Release Society
影响因子：
--
作者：
Milane L;Ganesh S;Shah S;Duan ZF;Amiji M
通讯作者：
Amiji M