Mechanism of drug resistance and reversal with ligustra-zine and cyclosporin a in cisplatin-induced human epithelial ovarian cancer resistant cell line 3AO/CDDP

2000 ◽  
Vol 12 (3) ◽  
pp. 197-203 ◽  
Author(s):  
Jian-li Chen ◽  
Sen Jiang ◽  
Rui-fang Yang ◽  
Fu-sheng Liu ◽  
Xiao-ming Sun
2020 ◽  
Vol 21 (7) ◽  
pp. 2619 ◽  
Author(s):  
Dominika Kazmierczak ◽  
Karol Jopek ◽  
Karolina Sterzynska ◽  
Barbara Ginter-Matuszewska ◽  
Michal Nowicki ◽  
...  

Ovarian cancer rates the highest mortality among all gynecological malignancies. The main reason for high mortality is the development of drug resistance. It can be related to increased expression of drug transporters and increased expression of extracellular matrix (ECM) proteins. Our foremost aim was to exhibit alterations in the miRNA expression levels in cisplatin (CIS), paclitaxel (PAC), doxorubicin (DOX), and topotecan (TOP)—resistant variants of the W1 sensitive ovarian cancer cell line—using miRNA microarray. The second goal was to identify miRNAs responsible for the regulation of drug-resistant genes. According to our observation, alterations in the expression of 40 miRNAs were present. We could observe that, in at least one drug-resistant cell line, the expression of 21 miRNAs was upregulated and that of 19 miRNAs was downregulated. We identified target genes for 22 miRNAs. Target analysis showed that miRNA regulates key genes responsible for drug resistance. Among others, we observed regulation of the ATP-binding cassette subfamily B member 1 gene (ABCB1) in the paclitaxel-resistant cell line by miR-363 and regulation of the collagen type III alpha 1 chain gene (COL3A1) in the topotekan-resistant cell line by miR-29a.


2019 ◽  
Author(s):  
Dominika Kazmierczak ◽  
Karol Jopek ◽  
Karolina Sterzynska ◽  
Marcin Rucinski ◽  
Radoslaw Januchowski

ABSTRACTOvarian cancer is the most fatal type of gynecological cancer. The main reason for high mortality is the development of drug resistance. It can be related to increased expression of drug transporters and increased expression of extracellular matrix (ECM) proteins. miRNA is a short noncoding RNA that regulates expression of about 60% of genes in the human genome and plays a crucial role in developing cancer, including resistance to chemotherapy.Our foremost aim was to exhibit alterations in the miRNA expression levels in the cisplatin (CIS), paclitaxel (PAC), doxorubicin (DOX), and topotecan (TOP) - resistant variants of W1 sensitive ovarian cancer cell line using miRNA microarray. The second goal was to identify miRNAs responsible for the regulation of drug-resistant genes.According to our observation, alterations in the expression of 40 miRNA genes. The level of expression of 21 genes was upregulated in at least one drug-resistant cell line. The expression of 19 genes was downregulated in at least one drug-resistant cell line. We identified target genes for 22 miRNAs. Target analysis showed that miRNA regulates key genes responsible for drug resistance. Among others, we observed regulation of the ABCB1 (MDR1) gene in the W1PR1 cell line by miR-363 and regulation of the COL3A1 gene in the W1TR cell line by miR-29a.Hence, on the basis of our findings, results indicate that genes responsible for drug resistance development in ovarian cancer can be regulated by miRNA.


2016 ◽  
Vol 16 (3) ◽  
pp. 226-237 ◽  
Author(s):  
Cristina P.R. Xavier ◽  
Milica Pesic ◽  
M. Helena Vasconcelos

2009 ◽  
Vol 33 (8) ◽  
pp. 1114-1119 ◽  
Author(s):  
Xueshi Ye ◽  
Ting Liu ◽  
Yuping Gong ◽  
Bohui Zheng ◽  
Wentong Meng ◽  
...  

Author(s):  
Jingjing Zhang ◽  
Jin Zhao ◽  
Wenjing Zhang ◽  
Guanyuan Liu ◽  
Dongmei Yin ◽  
...  

Author(s):  
Bahire Kucukkaya ◽  
Demet Erdag ◽  
Fahri Akbas ◽  
Leman Yalcintepe

Aim: Anticancer drugs (chemotherapeutics) used in cancer treatment (chemotherapy) lead to drug resistance. This study was conducted to investigate the possible effect of iron on calcium homeostasis in epithelial ovarian cancer cells (MDAH-2774) and cisplatin-resistant cells of the same cell line (MDAH-2774/DDP). Methods: To develop MDAH-2774/DDP cells, MDAH-2774 (MDAH) cells were treated with cisplatin in dose increases of 5 μM between 0 μM and 70 μM. The effect of iron on the viability of MDAH and MDAH/DDP cells was determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide test at the end of 24 h incubation. Results: At increasing iron concentrations in MDAH and MDAH/DDP cells, the mRNA gene of fifteen genes [inositol 1,4,5-triphosphate receptor (IP3R)1/2/3, ryanodine receptor (RYR)1/2, sarco/endoplasmic reticulum Ca2+ ATPase (SERCA)1/2/3, Na+/Ca2+ exchange (NCX)1/2/3, and plasma membrane Ca2+ ATPase (PMCA)1/2/3/4] associated with Ca2+ differences in expression were determined by quantitative reverse transcription-polymerase chain reaction. Changes in IP3R2, RYR1, SERCA2, NCX3, PMCA1, and PMCA3 gene expressions were observed in iron treatment of MDAH/DDP cells, while changes were detected in iron treatment of MDAH cells in IP3R1/2/3, RYR1/2, SERCA1/2/3, NCX2/3, and PMCA1 expressions. Conclusions: This changes in the expression of calcium channels, pumps, and exchange proteins in the epithelial ovarian cancer cell line and in cisplatin-resistant epithelial ovarian cancer cells suggest that iron may have an important role in regulating calcium homeostasis. Due to differences in the expression of genes that play of an important role in the regulation of calcium homeostasis in the effect of iron, drug resistance can be prevented by introducing a new perspective on the use of inhibitors and activators of these genes and thus cytostatic treatment strategies.


Genes ◽  
2018 ◽  
Vol 9 (8) ◽  
pp. 390
Author(s):  
Tomoyoshi Komiyama ◽  
Atsushi Ogura ◽  
Takehito Kajiwara ◽  
Yoshinori Okada ◽  
Hiroyuki Kobayashi

Various gene alterations related to acute leukemia are reported to be involved in drug resistance. We investigated idarubicin (IDR) resistance using exome nuclear DNA analyses of the human acute leukemia cell line MOLT-3 and the derived IDR-resistant cell line MOLT-3/IDR. We detected mutations in MOLT-3/IDR and MOLT-3 using both Genome Analysis Toolkit (GATK) and SnpEff program. We found 8839 genes with specific mutations in MOLT-3/IDR and 1162 genes with accompanying amino acid mutations. The 1162 genes were identified by exome analysis of polymerase-related genes using Kyoto Encyclopedia of Genes and Genomes (KEGG) and, among these, we identified genes with amino acid changes. In resistant strains, LIG and helicase plurality genes showed amino-acid-related changes. An amino acid mutation was also confirmed in polymerase-associated genes. Gene ontology (GO) enrichment testing was performed, and lipid-related genes were selected from the results. Fluorescent activated cell sorting (FACS) was used to determine whether IDR permeability was significantly different in MOLT-3/IDR and MOLT-3. The results showed that an IDR concentration of 0.5 μg/mL resulted in slow permeability in MOLT-3/IDR. This slow IDR permeability may be due to the effects of amino acid changes in polymerase- and lipid-associated genes.


2020 ◽  
Vol 11 (5) ◽  
pp. 1129-1138
Author(s):  
Tao Yu ◽  
Qian Xia ◽  
Ting Gong ◽  
Jing Wang ◽  
DianSheng Zhong

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