Screening of biochemical modulator by tumor cell permeability of doxorubicin
Screening of biochemical modulator by tumor cell permeability of doxorubicin
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DOI：
10.1016/j.ijpharm.2007.10.015
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发表时间：
2008-04-16
影响因子：
5.8
通讯作者：
Sonobe, Takashi
中科院分区：
文献类型：
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作者：
Sadzuka, Yasuyuki;Hatakeyama, Haruna;Sonobe, Takashi
我们筛选了各种食品成分在体外抑制肿瘤细胞阿霉素 (DOX) 渗透性的能力，目的是寻找新型调节剂。尽管辣椒素衍生物姜辣素和阿魏酸倾向于促进 DOX 外流，但辣椒素不会改变肿瘤细胞中的 DOX 通透性。这些成分与 DOX 的组合也无效。相反，葫芦素E显着促进DOX流入肿瘤细胞并增加肿瘤细胞中的DOX浓度。此外，联合葫芦素 E 显着抑制肿瘤细胞中 DOX 的流出，并显示可以维持肿瘤细胞中的 DOX 水平。还证实葫芦素 E 与 DOX 的组合对培养的肿瘤细胞产生有效的细胞毒性。此外，与单独治疗相比，葫芦素 E 和 DOX 的组合显示出更高的细胞毒性。在体内，与对照水平相比，单独使用 DOX 治疗不会改变 M5076 卵巢肉瘤的肿瘤大小或肿瘤重量的时间进程。相反，与单独使用DOX组相比，葫芦素E与DOX的组合导致肿瘤大小和重量减小，表明具有有效的抗肿瘤活性。总之，葫芦素E与DOX的联合可能是癌症化疗中治疗应用的有效工具。 (C) 2007 Elsevier B.V. 保留所有权利。
We screened various food components for their ability to inhibit doxorubicin (DOX) permeability in tumor cells in vitro with the aim of finding novel modulators. Capsaicin did not change DOX permeability in the tumor cells, although the capsaicin derivatives gingerol and ferulic acid tended to promote DOX efflux. Combinations of these components with DOX were also not effective. In contrast, cucurbitacin E significantly promoted DOX influx into tumor cells and increased DOX concentration in tumor cells. Furthermore, combined cucurbitacin E significantly suppressed DOX efflux from tumor cells and was shown to maintain the DOX level in tumor cells. It was also confirmed that the combination of cucurbitacin E with DOX resulted in effective cytotoxicity for tumor cells in culture. Additionally, the combination of cucurbitacin E and DOX showed increased cytotoxicity when compared to each treatment alone. In vivo, DOX alone treatment did not change the time course of tumor size or tumor weight of M5076 ovarian sarcoma, compared to control levels. In contrast, the combination of cucurbitacin E with DOX resulted in decreased tumor size and tumor weight, compared to that in DOX alone group, indicating effective antitumor activity. In conclusion, the combination of cucurbitacin E with DOX may be an effective tool with treated application in the cancer chemotherapy. (C) 2007 Elsevier B.V. All rights reserved.