Aptamer-mediated survivin RNAi enables 5-fluorouracil to eliminate colorectal cancer stem cells.
Aptamer-mediated survivin RNAi enables 5-fluorouracil to eliminate colorectal cancer stem cells.
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DOI：
10.1038/s41598-017-05859-z
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发表时间：
2017-07-19
影响因子：
4.6
通讯作者：
Duan W
中科院分区：
文献类型：
--
作者：
AlShamaileh H;Wang T;Xiang D;Yin W;Tran PH;Barrero RA;Zhang PZ;Li Y;Kong L;Liu K;Zhou SF;Hou Y;Shigdar S;Duan W
化疗耐药的发展和无法消除癌症干细胞是癌症化疗的关键限制之一。为了未来对癌症的有效治疗，迫切需要能够克服这些限制的新的分子治疗策略。在这份报告中，我们证明了EPCAM-适体引导的Survivin RNAi在体外和小鼠结直肠癌异种移植模型中都有效地下调了Survivin的表达。当与常规化疗药物联合使用时，适体导向的Survivin RNAi能够增强结直肠癌干细胞对5-FU或奥沙利铂的敏感性，增加细胞凋亡，抑制肿瘤生长，并提高荷瘤鼠的总体生存时间。我们的结果表明Survivin是结直肠癌干细胞先天耐药的关键分子之一。因此，适体介导的肿瘤干细胞靶向Survivin与化疗药物的结合构成了一条改善肿瘤临床治疗结果的新途径。
The development of chemoresistance and inability in elimination of cancer stem cells are among the key limitations of cancer chemotherapy. Novel molecular therapeutic strategies able to overcome such limitations are urgently needed for future effective management of cancer. In this report, we show that EpCAM-aptamer-guided survivin RNAi effectively downregulated survivin both in colorectal cancer cells in vitro and in a mouse xenograft model for colorectal cancer. When combined with the conventional chemotherapeutic agents, the aptamer-guided survivin RNAi was able to enhance the sensitivity towards 5-FU or oxaliplatin in colorectal cancer stem cells, increase apoptosis, inhibit tumour growth and improve the overall survival of mice bearing xenograft colorectal cancer. Our results indicate that survivin is one of the key players responsible for the innate chemoresistance of colorectal cancer stem cells. Thus, aptamer-mediated targeting of survivin in cancer stem cells in combination with chemotherapeutic drugs constitutes a new avenue to improve treatment outcome in oncologic clinics.
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DOI：
10.1042/bj20100814
发表时间：
2010-09-01
期刊：
The Biochemical journal
影响因子：
--
作者：
Altieri DC
通讯作者：
Altieri DC
影响因子：
37.3
作者：
Martowicz A;Rainer J;Lelong J;Spizzo G;Gastl G;Untergasser G
通讯作者：
Untergasser G
影响因子：
8.4
作者：
Li, Jie;Hou, Ni;Kuwano, Hiroyuki
通讯作者：
Kuwano, Hiroyuki
体外球状培养物从黑色素瘤细胞系中诱导出高度分化但致瘤的细胞群
影响因子：
2.2
作者：
Mo, Jing;Sun, Baocun;Sun, Ran
通讯作者：
Sun, Ran
影响因子：
13.6
作者：
Huang EH;Wicha MS
通讯作者：
Wicha MS