Increase in docetaxel-resistance of ovarian carcinoma-derived RMG-1 cells with enhanced expression of Lewis Y antigen.

Increase in docetaxel-resistance of ovarian carcinoma-derived RMG-1 cells with enhanced expression of Lewis Y antigen.
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Lewis Y 抗原表达增强,卵巢癌 RMG-1 细胞对多西紫杉醇的耐药性增加

DOI:
10.3390/ijms12117323
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发表时间:
2011
影响因子:
5.6
通讯作者:
Iwamori M
Iwamori M
中科院分区:
生物学2区
文献类型:
--
作者:
Zhang F;Liu J;Lin B;Liu Q;Zhao Y;Zhu L;Hao Y;Zhang S;Iwamori M

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卵巢上皮癌是妇科恶性肿瘤中死亡率最高的。研究发现糖脂或碳水化合物的代谢与癌细胞获得抗癌药物抗性有关。本研究旨在探讨刘易斯Y(LeY)抗原在肿瘤细胞耐药中的作用。我们将α 1,2-岩藻糖基转移酶基因转染人卵巢癌RMG-1细胞,建立了LeY表达增强的RMG-1-hFUT细胞。MTT法检测多西紫杉醇对细胞存活的影响,流式细胞仪和透射电镜观察多西紫杉醇对细胞凋亡的影响。RMG-1-hFUT细胞的质膜和胞内颗粒被抗LeY抗体染色,染色强度高于对照细胞。RMG-1-hFUT细胞在多西他赛浓度和时间过程方面表现出比对照细胞更高的多西他赛抗性。用10 μg/mL多西他赛处理72 h后,对照细胞(而非RMG-1-hFUT)由于细胞骨架的解体而含有大量阳性染色的细胞碎片。在透射电子显微镜下,尽管如上所述用多西他赛处理的对照细胞显示以下形态,即,在凋亡过程中,RMG-1-hFUT细胞的绒毛消失,细胞缩小,核固缩,染色质凝集,细胞芽含核,细胞质中仅可见染色质凝集和空泡。总之,LeY表达增强的细胞显示获得紫杉醇耐药性,表明糖缀合物可能参与耐药性。
Epithelial carcinomas of the ovary exhibit the highest mortality rate among gynecologic malignancies. Studies found that the metabolism of glycolipids or carbohydrates is associated with acquirement of anticancer drug-resistance by cancer cells. This study was to characterize possible involvement of Lewis Y (LeY) antigen in the drug-resistance of cancer cells. We transfected the α1,2-fucosyltransferase gene into human ovarian carcinoma-derived RMG-1 cells and established RMG-1-hFUT cells with enhanced expression of LeY. We determined the effects of docetaxel on the survival of cells by MTT assaying and observed the apoptosis of cells in the presence of docetaxel by flow cytometric analysis and by transmission electron microscopy. Plasma membranes and intracellular granules in RMG-1-hFUT cells were stained with anti-LeY antibody, the intensity of the staining was higher than that in control cells. The RMG-1-hFUT cells exhibited higher resistance to docetaxel than the control cells with regard to the docetaxel concentration and time course. After treatment with 10 μg/mL docetaxel for 72 h, the control cells, but not RMG-1-hFUT, contained abundant positively stained cell debris due to disintegration of the cytoskeleton. On transmission electron microscopy, although the control cells treated with docetaxel as above showed the following morphology, i.e., absence of villi, cells shrunken in size, pyknosis, agglutinated chromatin and cell buds containing nuclei in the process of apoptosis, the RMG-1-hFUT cells showed only agglutinated chromatin and vacuoles in the cytoplasm. In summary, cells with enhanced expression of LeY were shown to acquire docetaxel-resistance, indicating the possible involvement of glycoconjugates in the drug-resistance.
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