State Key Laboratory of Biotherapy, Section of Signal Transduction and Molecular Targeted Therapy, West China Hospital, Sichuan University, No,1 Ke Yuan 4 Lu, Chengdu, 610041, China.
Breast Cancer Res. 2010;12(1):R8. doi: 10.1186/bcr2473. Epub 2010 Jan 15.
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.
紫杉醇（Taxol）是一种广泛用于癌症治疗的微管靶向药物。然而，临床中经常会遇到对紫杉醇的耐药性。人们越来越关注寻找可能增加常规化疗药物敏感性的化合物。在这项研究中，我们研究了绿茶多酚（-）-表没食子儿茶素没食子酸酯（EGCG）是否能使乳腺癌细胞对紫杉醇在体内敏感。
用或不用 EGCG 和紫杉醇处理乳腺癌细胞，然后检测细胞存活和凋亡。用 Western blot 检测 c-Jun NH2-末端激酶（JNK）磷酸化和葡萄糖调节蛋白 78（GRP78）表达。在体内研究中，将 4T1 乳腺癌细胞接种到 Balb/c 小鼠中建立移植模型。用或不用 EGCG（30mg/kg，腹腔注射）和紫杉醇（10mg/kg，腹腔注射）处理荷瘤小鼠。监测肿瘤生长。检测肿瘤组织中的细胞凋亡。用 Western blot 分析肿瘤细胞裂解物中 GRP78 表达和 JNK 磷酸化。
EGCG 协同增强了乳腺癌细胞对紫杉醇的体外和体内敏感性。与单一药物治疗相比，EGCG 联合紫杉醇显著诱导 4T1 细胞凋亡。当荷瘤小鼠用紫杉醇联合 EGCG 治疗时，肿瘤生长明显受到抑制，而紫杉醇或 EGCG 的单一药物活性较差。EGCG 克服了紫杉醇诱导的 4T1 细胞中 GRP78 表达，并增强了紫杉醇诱导的 JNK 磷酸化，无论是在体外还是在体内。
EGCG 可用作增敏剂来增强紫杉醇的细胞毒性。
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