Gestational Trophoblastic Neoplasia (GTN) is a term used for a group of malignant gynecological tumors including choriocarcinoma. Low-risk neoplasias can be cured using single agents Methotrexate (MTX) and actinomycin-D (ACD), but in certain cases, decreased responsiveness and serious side effects occur. Therefore, researchers have been attempting to find new treatment modalities. One of the most popular way for increasing cancer patient survival rates is supporting treatment with adjuvant molecules or chemosensitizers. For this purpose, we investigated epigallocatechin-3-gallate (EGCG), a green tea cathecin, and Erlotinib, an EGFR tyrosine kinase inhibitor, as single agents and combined with MTX or ACD. In accordance with this, JAR (human placenta choriocarcinoma) cell line was used as an in vitro model and MTT, LDH, caspase-3 activation, RT-PCR, and Western Blot analyses were performed to investigate the effects of the test materials. Our studies demonstrate that combination of Erlotinib and EGCG with MTX and ACD decreases JAR cell proliferation and metastatic HER2 protein synthesis and increases caspase-3 activation compared to ACD or MTX alone. In addition, significant increase was observed in the apoptotic Bax gene, but no notable protein synthesis occurred in the Western Blot analysis, which suggests that combination of Erlotinib and EGCG with classical chemotherapeutics ACD or MTX may lead the JAR cells to apoptosis, but not by a mitochondrial pathway. All the results indicate that the synergetic effect of Erlotinib and EGCG with classical chemotherapeutics may help to increase patient survival rates of choriocarcinoma, but the detailed mechanism needs further investigation.

译文

妊娠滋养细胞肿瘤(GTN)是一个术语,用于表示包括绒癌在内的一系列恶性妇科肿瘤。可以使用甲氨蝶呤(MTX)和放线菌素D(ACD)单一药物治愈低危的肿瘤,但在某些情况下,会降低反应性和严重的副作用。因此,研究人员一直在尝试寻找新的治疗方式。增加癌症患者存活率的最流行方法之一是支持使用辅助分子或化学增敏剂进行治疗。为此,我们研究了绿茶儿茶素表没食子儿茶素-3-没食子酸酯(EGCG)和EGFR酪氨酸激酶抑制剂厄洛替尼作为单一药物并与MTX或ACD联合使用。据此,将JAR(人胎盘绒毛膜癌)细胞系用作体外模型,并进行MTT,LDH,caspase-3激活,RT-PCR和Western Blot分析以研究测试材料的作用。我们的研究表明,与单独使用ACD或MTX相比,厄洛替尼和EGCG与MTX和ACD的组合可降低JAR细胞增殖和转移性HER2蛋白的合成,并增加caspase-3激活。此外,凋亡的Bax基因显着增加,但在Western Blot分析中未发现明显的蛋白质合成,这表明厄洛替尼和EGCG与经典化学疗法ACD或MTX的组合可能导致JAR细胞凋亡,但并非通过线粒体途径。所有结果表明,厄洛替尼和EGCG与经典化学疗法的协同作用可能有助于提高绒毛膜癌的患者生存率,但详细的机制尚需进一步研究。

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