Resistance of cholangiocarcinoma cells to parthenolide-induced apoptosis by the excretory-secretory products of Clonorchis sinensis
Resistance of cholangiocarcinoma cells to parthenolide-induced apoptosis by the excretory-secretory products of Clonorchis sinensis
复制标题
DOI：
10.1007/s00436-008-1283-y
复制
发表时间：
2009-04-01
影响因子：
2
通讯作者：
Bae, Young Mee
中科院分区：
文献类型：
--
作者：
Kim, Young Ju;Choi, Min-Ho;Bae, Young Mee
华支睾吸虫（中国或东方肝吸虫）的感染是发生胆管癌（一种人类肝内胆管上皮癌）的重要危险因素。小白菊内酯是一种倍半萜内酯，具有很强的抗癌特性，并且还可以诱导胆管癌细胞凋亡。许多研究人员报告说，中华线虫和维韦里后睾吸虫的排泄分泌（ES）产物可促进胆管癌的发展。然而，其内在机制尚不清楚。因此，我们研究了 ES 产品在胆管癌细胞系 HuCCT1 中的生物学作用。中华茶树的 ES 产物增加 HuCCT1 细胞的增殖并增强环氧合酶 (COX)-2 的表达。为了确定用 ES 产品处理的细胞对小白菊内酯的反应是否不同，HuCCT1 细胞单独用小白菊内酯处理，或在用 ES 产品预处理后用小白菊内酯处理。用 ES 产品预处理的细胞对小白菊内酯诱导的细胞凋亡具有抵抗力。由于小白菊内酯已被报道为COX-2抑制剂，因此我们推测COX-2可能是促进胆管癌细胞对小白菊内酯诱导的细胞凋亡产生抵抗的关键因素。这些结果表明，应调整中华支线虫感染的胆管癌患者的化疗方案，以考虑肝吸虫分泌的 ES 产物。
Infection by Clonorchis sinensis, the Chinese or oriental liver fluke, is a significant risk factor for the development of cholangiocarcinoma, a human epithelial carcinoma of the intrahepatic bile duct. Parthenolide is a sesquiterpene lactone that has strong anticancer properties and is also known to induce apoptosis in cholangiocarcinoma cells. Many investigators have reported that excretory-secretory (ES) products of C. sinensis as well as Opisthorchis viverrini promote the development of cholangiocarcinomas. However, the intrinsic mechanism is not clearly understood. Therefore, we investigated the biological roles of the ES products in a cholangiocarcinoma cell line, HuCCT1. The ES products of C. sinensis increased proliferation of HuCCT1 cells and augmented the expression of cyclooxygenase (COX)-2. To determine whether cells treated with ES products would respond differently to parthenolide, HuCCT1 cells were treated with parthenolide alone or parthenolide after pretreatment with ES products. Cells pretreated with ES products were resistant to parthenolide-induced apoptosis. Because parthenolide has been reported to be a COX-2 inhibitor, we hypothesize that COX-2 might be a key factor that promotes resistance of cholangiocarcinoma cancer cells to parthenolide-induced apoptosis. These results suggest that chemotherapy treatment regimens in cholangiocarcinoma patients with C. sinensis infection should be modulated to account for ES products excreted by the liver fluke.