Metabolism targeting therapy of dichloroacetate-loaded electrospun mats on colorectal cancer
Metabolism targeting therapy of dichloroacetate-loaded electrospun mats on colorectal cancer
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负载二氯乙酸的电纺垫对结直肠癌的代谢靶向治疗
DOI：
10.3109/10717544.2013.870258
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发表时间：
2015-01
期刊：
影响因子：
6
通讯作者：
Huang Yubin
中科院分区：
文献类型：
--
作者：
Wang Feifei;Yue Jun;Jing Xiabin;Huang Yubin
摘要 肿瘤细胞和正常细胞之间能量代谢的差异为肿瘤治疗药物靶点的研究提供了一个有吸引力的途径。使用原位施用代谢调节剂（二氯乙酸钠，DCA）来逆转肿瘤细胞的“瓦伯格效应”已被证明是一种有效的肿瘤治疗方法。在此，将 DCA 和二氯乙酸二异丙胺 (DADA) 分别掺入聚交酯 (PLA) 电纺垫中，并通过原位给药应用于 C26 荷瘤小鼠。治疗12天后，DC组（用负载DCA的垫处理）和DA组（用负载DADA的垫处理）的肿瘤抑制率分别达到75％和84％。 DA组在高局部浓度下具有可耐受的生理毒性，治疗15天后抑瘤率达95%，无复发。这些代谢调节剂的理想治疗效果应归因于 DCA 和 DADA 的能量中心代谢靶向作用，这在体外和体内都得到了证明。因此，负载 DCA 和 DADA 的垫子是区分肿瘤细胞和正常细胞以最大程度地减少全身毒性的有效抗癌药物剂量。
Abstract Differences in energy metabolism between tumor cells and normal cells offer an attractive avenue of research into drug targets for tumor therapy. The use of a metabolic modulator (sodium dichloroacetate, DCA), administered in situ, to reverse the “Warburg effect” of tumor cells has been demonstrated as an effective tumor therapy. Herein, DCA and diisopropylamine dichloroacetate (DADA) were incorporated separately into polylactide (PLA) electrospun mats and applied to C26 tumor-bearing mice via in situ administration. After 12 d of treatment, the tumor suppression rates of 75% and 84% were achieved in the DC group (treated with a DCA-loaded mat) and the DA group (treated with a DADA-loaded mat), respectively. With tolerable physiologic toxicity under high local concentration, the DA group showed a 95% tumor suppression rate without any recurrence after 15 d of therapy. The desirable therapeutic effects of these metabolic modulators should ascribe to the energy-central metabolism-targeting effects of DCA and DADA, which were demonstrated both in vitro and in vivo. Therefore, DCA- and DADA-loaded mats are the effective anti-cancer drugs dosages to discriminate between tumor cells and normal cells for minimizing systemic toxicity.
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二氯乙酸 (DCA) 与携带 MDA-7/IL-24 的溶瘤腺病毒结合可增强肿瘤细胞死亡
影响因子：
4.3
作者：
Niu, Na;Xiao, Lianli;Wang, Yigang;Qian, Jing;Li, Xin;Xie, Guoliang
通讯作者：
Xie, Guoliang
影响因子：
8.8
作者：
Michelakis, E. D.;Webster, L.;Mackey, J. R.
通讯作者：
Mackey, J. R.
影响因子：
3.8
作者：
Sun, Ramon C.;Fadia, Mitali;Blackburn, Anneke C.
通讯作者：
Blackburn, Anneke C.
影响因子：
13.5
作者：
BELLENTANI, S;TIRIBELLI, C;SASSATELLI, R
通讯作者：
SASSATELLI, R
DOI：
10.1073/pnas.0611662104
发表时间：
2007-05-29
影响因子：
11.1
作者：
Cairns, Rob A.;Papandreou, Ioanna;Denko, Nicholas C.
通讯作者：
Denko, Nicholas C.