Involvement of the MDR1 gene and glycolipids in anticancer drug-resistance of human ovarian carcinoma-derived cells
Involvement of the MDR1 gene and glycolipids in anticancer drug-resistance of human ovarian carcinoma-derived cells
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DOI：
10.1007/s13577-019-00261-5
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发表时间：
2019-07
期刊：
影响因子：
4.3
通讯作者：
Kyoko Tanaka;K. Kiguchi;M. Mikami;D. Aoki;M. Iwamori
中科院分区：
文献类型：
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作者：
Kyoko Tanaka;K. Kiguchi;M. Mikami;D. Aoki;M. Iwamori
我们以前曾报道，耐紫杉醇的卵巢癌细胞表达MDR1(多药耐药1)基因，糖脂合成增强，即LacCer、Gb3Cer、Leband GM3，而抗顺铂耐药细胞丢失GM3。为了进一步研究糖脂和mdr1基因在卵巢癌耐药中的作用，我们检测了几种卵巢癌来源细胞，即浆液性KF28细胞、粘液性HMKOA细胞、子宫内膜样HNOA细胞和透明细胞RMG-1细胞中糖脂和mdr1基因的表达及其对抗癌药物的敏感性。仅在RMG-1细胞中检测到mdr1基因，其中Gb4Cer和Leband GM3的含量高于其他细胞，这反映了RMG-1细胞对紫杉醇和多西紫杉醇的耐药性比其他细胞高。在均不表达mdr1基因的HNOA、HMKOA和KF28细胞中，HNOA和HMKOA细胞对紫杉醇和多西紫杉醇的耐受性相对较强，并且含有7倍以上的Gb4Cer和Lebin KF28细胞，这表明含有较长糖链的糖脂细胞即使不表达mdr1基因，也具有对疏水药物的耐药性。相反，GM3含量最高的RMG-1细胞对顺铂的敏感性相对较高，这可能是由于与顺铂结合的负电荷所致。提示MDR1、Gb4Cer、Leband GM3的表达增加可能参与了紫杉醇和多西紫杉醇对疏水性紫杉醇和多西紫杉醇的耐药，GM3与碱性顺铂的耐药有关。
We previously reported that anti-paclitaxel-resistant ovarian carcinoma cells characteristically expressed the MDR1 (multidrug resistance 1) gene with enhanced synthesis of glycolipids, i.e., LacCer, Gb3Cer, Leband GM3, and that anti-cisplatin-resistant cells lost GM3. To further examine the involvement of glycolipids and the MDR1 gene in the anticancer drug-resistance, we determined their expression and the sensitivity to anticancer drugs of several ovarian carcinoma-derived cells, i.e., serous KF28, mucinous HMKOA, endometrioid HNOA and clear cell RMG-1 cells. The MDR1 gene was only detected in RMG-1 cells, in which the amounts of Gb4Cer, Leband GM3 were higher than in the other cells, which reflected their much higher resistance to paclitaxel and docetaxel compared to the other cells. Among HNOA, HMKOA and KF28 cells, all of which did not express the MDR1 gene, the HNOA and HMKOA cells were relatively more resistant to paclitaxel and docetaxel than KF28 cells, and contained more than sevenfold Gb4Cer and Lebin KF28 cells, indicating that cells containing glycolipids with longer carbohydrate chains, even without expression of the MDR1 gene, have the resistance property as to hydrophobic drugs. On the contrary, RMG-1 cells with the highest amount of GM3 were relatively more sensitive to cisplatin than the other cells, which probably due to a negative charge for binding with cisplatin. Thus, MDR1, and increased amounts of Gb4Cer, Leband GM3 were suggested to be involved in the anticancer drug-resistance to hydrophobic paclitaxel and docetaxel, and GM3 was to basic cisplatin.