Takezaki Yuka, Namikawa Tsutomu, Koyama Tsuyoshi, Munekage Eri, Munekage Masaya, Maeda Hiromichi, Kitagawa Hiroyuki, Hanazaki Kazuhiro
Department of Surgery, Kochi Medical School Hospital, Kochi, Japan.
Department of Surgery, Kochi Medical School Hospital, Kochi, Japan
Anticancer Res. 2016 Nov;36(11):6077-6082. doi: 10.21873/anticanres.11197.
BACKGROUND/AIM: One reason of poor survival rate of patients with pancreatic cancer is the development of chemoresistance. The aim of the present study was to investigate the effects of eribulin mesylate in gemcitabine-refractory advanced pancreatic cancer cell lines.
Three human pancreatic cancer cell lines (AsPC-1, Panc-1, and SUIT-2) and human pancreatic endoderm (hPE) cells were used to evaluate the antitumor effects of gemcitabine and eribulin mesylate. Cell viability after treatment of cells with different concentrations of gemcitabine and eribulin mesylate was evaluated using water-soluble tetrazolium salts (WST) assays; cytotoxic effects were evaluated on the basis of morphological changes to cells.
Gemcitabine had no effect on cell viability of AsPC-1 nor Panc-1 cells, whereas gemcitabine reduced cell viability of SUIT-2 cells in a dose-dependent manner. Eribulin mesylate significantly reduced cell viability of both AsPC-1 and Panc-1 cells (p<0.001 and p=0.002, respectively), but had no effect on hPE cells. Microscopic examination of AsPC-1 and Panc-1 cells after treatment with eribulin mesylate revealed morphological changes that included cell shrinkage, membrane blebbing, and fragmentation of the cells after drug exposure, and these were concentration-dependent effects.
The findings of the present study suggest that eribulin mesylate may be a promising potential anticancer drug for gemcitabine-refractory advanced pancreatic cancer.
背景/目的：胰腺癌患者生存率低的一个原因是化疗耐药性的产生。本研究的目的是探讨甲磺酸艾瑞布林对吉西他滨难治性晚期胰腺癌细胞系的影响。
使用三种人胰腺癌细胞系（AsPC-1、Panc-1和SUIT-2）以及人胰腺内胚层（hPE）细胞来评估吉西他滨和甲磺酸艾瑞布林的抗肿瘤作用。使用水溶性四氮唑盐（WST）试验评估用不同浓度的吉西他滨和甲磺酸艾瑞布林处理细胞后的细胞活力；根据细胞的形态变化评估细胞毒性作用。
吉西他滨对AsPC-1细胞和Panc-1细胞的细胞活力均无影响，而吉西他滨以剂量依赖的方式降低了SUIT-2细胞的细胞活力。甲磺酸艾瑞布林显著降低了AsPC-1细胞和Panc-1细胞的细胞活力（分别为p<0.001和p=0.002），但对hPE细胞无影响。在用甲磺酸艾瑞布林处理后对AsPC-1细胞和Panc-1细胞进行显微镜检查发现，形态学变化包括细胞收缩、细胞膜起泡以及药物暴露后细胞破碎，这些都是浓度依赖性效应。
本研究结果表明，甲磺酸艾瑞布林可能是一种有前景的用于吉西他滨难治性晚期胰腺癌的潜在抗癌药物。
