(-)-Epigallocatechin gallate sensitizes breast cancer cells to paclitaxel in a murine model of breast carcinoma.
(-)-Epigallocatechin gallate sensitizes breast cancer cells to paclitaxel in a murine model of breast carcinoma.
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(-)-表没食子儿茶素没食子酸酯使小鼠乳腺癌模型中的乳腺癌细胞对紫杉醇敏感
DOI：
10.1186/bcr2473
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发表时间：
2010
期刊：
影响因子：
--
通讯作者：
Jiang Y
中科院分区：
文献类型：
--
作者：
Luo T;Wang J;Yin Y;Hua H;Jing J;Sun X;Li M;Zhang Y;Jiang Y
紫杉醇（Taxol®）是一种微管靶向药物，广泛用于癌症治疗。然而，紫杉醇耐药在临床上经常遇到。人们对鉴定可增加对常规化疗剂的敏感性的化合物越来越感兴趣。在这项研究中，我们探讨了绿色茶多酚（-）-表没食子儿茶素没食子酸酯（EGCG）是否可以增敏乳腺癌紫杉醇在体内。乳腺癌细胞用或不用表没食子儿茶素没食子酸酯和紫杉醇处理，随后检测细胞存活和凋亡。Western blotting检测c-Jun氨基末端激酶（JNK）磷酸化和葡萄糖调节蛋白78（GRP 78）表达。在体内研究中，将4 T1乳腺癌细胞接种到Balb/c小鼠中以建立移植模型。将荷瘤小鼠用或不用EGCG（30 mg/kg，i. p.）和紫杉醇（10 mg/kg，i. p.）。监测肿瘤生长。检测肿瘤组织细胞凋亡。对来自肿瘤的细胞裂解物进行GRP 78表达和JNK磷酸化的Western印迹分析。表没食子儿茶素没食子酸酯协同增敏乳腺癌细胞紫杉醇在体外和体内。EGCG与紫杉醇联合应用较单独应用能显著诱导4 T1细胞凋亡。当用紫杉醇与EGCG组合治疗荷瘤小鼠时，肿瘤生长被显著抑制，而紫杉醇或EGCG的单药活性较差。在体外和体内4 T1细胞中，EGCG克服了紫杉醇诱导的GRP 78表达，并增强了紫杉醇诱导的JNK磷酸化。表没食子儿茶素没食子酸酯可用作增敏剂以增强紫杉醇的细胞毒性。
Paclitaxel (Taxol®) is a microtubule-targeted agent that is widely used for cancer treatment. However, resistance to paclitaxel is frequently encountered in the clinic. There is increasing interest in identifying compounds that may increase the sensitivity to conventional chemotherapeutic agents. In this study, we investigated whether green tea polyphenol (-)-epigallocatechin gallate (EGCG) could sensitize breast carcinoma to paclitaxel in vivo. Breast cancer cells were treated with or without EGCG and paclitaxel followed by detection of cell survival and apoptosis. c-Jun NH2-terminal kinase (JNK) phosphorylation and glucose-regulated protein 78 (GRP78) expression were detected by Western blotting. For in vivo study, 4T1 breast cancer cells were inoculated into Balb/c mice to establish a transplantation model. The tumor-bearing mice were treated with or without EGCG (30 mg/kg, i.p.) and paclitaxel (10 mg/kg, i.p.). Tumor growth was monitored. Apoptosis in tumor tissues was detected. Cell lysates from tumors were subjected to Western blot analysis of GRP78 expression and JNK phosphorylation. EGCG synergistically sensitized breast cancer cells to paclitaxel in vitro and in vivo. EGCG in combination with paclitaxel significantly induced 4T1 cells apoptosis compared with each single treatment. When tumor-bearing mice were treated with paclitaxel in combination with EGCG, tumor growth was significantly inhibited, whereas the single-agent activity for paclitaxel or EGCG was poor. EGCG overcame paclitaxel-induced GRP78 expression and potentiated paclitaxel-induced JNK phosphorylation in 4T1 cells both in vitro and in vivo. EGCG may be used as a sensitizer to enhance the cytotoxicity of paclitaxel.
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影响因子：
45.3
作者：
Nabholtz, JM;Gelmon, K;Winograd, B
通讯作者：
Winograd, B
DOI：
10.1083/jcb.91.2.479
发表时间：
1981-11
期刊：
The Journal of cell biology
影响因子：
--
作者：
Parness J;Horwitz SB
通讯作者：
Horwitz SB
影响因子：
9.7
作者：
Paschka, AG;Butler, R;Young, CYF
通讯作者：
Young, CYF
影响因子：
11.5
作者：
Andre, Fabrice;Hatzis, Christos;Pusztai, Lajos
通讯作者：
Pusztai, Lajos
影响因子：
4.7
作者：
Chen, C;Shen, GX;Kong, ANT
通讯作者：
Kong, ANT