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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 changes in the expression of many drug resistance genes as well as expression of extracellular matrix proteins and cell density in the tumor. We developed a simple two-dimensional and three-dimensional model of drug sensitive A2780 and resistant to cisplatin and paclitaxel variants of ovarian cancer cell line. Using MTT assay, we compared drug resistance in two-dimensional and three-dimensional cell culture conditions. Real-time polymerase chain reaction analysis was used to compare the expression of drug resistance genes. The expression of proteins in spheroids was determined by immunohistochemistry. We observed a moderate increase in cisplatin resistance and a significant increase in paclitaxel resistance between two-dimensional and three-dimensional cell culture conditions. Our findings show that changes in the expression of drug resistance genes may play a crucial role in the drug resistance of cancer cells in traditional cell culture. On the other hand, the drug resistance in spheroids may result from different mechanisms such as cell density in the spheroid, extracellular matrix proteins expression and drug capacity to diffuse into the spheroid., (Copyright © 2021 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Ovarian cancer is characterized by the higher mortality among gynecological cancers. In results of MDR development during chemotherapy cancer cells become resistant to further treatment. Microarray techniques can provide information about MDR development at gene expression level. ABC and SLC transporters are most important proteins responsible for this phenomenon. In this study changes of ABC and SLC genes expression pattern in drugs resistant sublines of the A2780 ovarian cancer cell line were demonstrated. The cytostatic resistant sublines were generated by culture of A2780 cell line with an increasing concentration of the indicated drugs. As screening methods, we used Affymetrix U219 Human Genome microarrays. Independent t-tests were used to determinate statistical significances of results. Genes that expression levels were higher than assumed threshold (upregulated above threefold and downregulated under -3 fold) were visualized using scatter plot method, selected and listed in table. Between the ABC genes increased expression of seven genes and decreased expression of three genes were observed. Expression of two genes was increased or decreased depending on the cell line. We observed significant (more than tenfold) increase in expression of four ABC genes: ABCA8, ABCB1, ABCB4 and ABCG2 and decreased expression of ABCA3 gene. We also observed changes in expression of 32 SLC genes. Between them we observe increased expression of 17 genes and decreased expression of 15 genes. Expression of four genes was increased or decreased dependent on cell line. The expression of nine SLC genes increased or decreased very significantly (more than tenfold). Five genes were significantly upregulated: SLC2A9, SLC16A3, SLC16A14, SLC38A4 and SLC39A8. Four additional genes were significantly downregulated: SLC2A14, SLC6A15, SLC8A1 and SLC27A2. Expression profiles of these genes give strong arguments for assumption of correlation between expression of ABC and SLC genes and drug resistance phenomenon. Identifying correlations between specific drug transporters and cytostatic drug resistance will require further investigation., (Copyright © 2014 Elsevier Masson SAS. All rights reserved.)

Multiple drug resistance is one of the main reasons for low chemotherapeutic efficiency in cancer patients. The proteins that are most frequently implicated to play a role in this mechanism are transmembrane proteins that are members of the ABC family. The most important ABC protein is MDR1 (ABCB1), which is expressed in over fifty percent of drug-resistant cancers. The phosphatidylcholine transporter, MDR3 (ABCB4), exhibits high homology with MDR1. An increasing body of evidence suggests that MDR3 plays a role in drug resistance. In the present study, we used doxorubicin-, paclitaxel- and vincristine-resistant cancer cell lines. A chemosensitivity assay MTT test was performed to assess drug resistance. Quantitative real-time polymerase chain reaction analyses were performed to determine the mRNA expression levels of the MDR1 and MDR3 genes. We observed dose-dependent responses to doxorubicin, paclitaxel and vincristine in the investigated cell lines. In all of the drug-resistant cell lines that we studied, we observed increased MDR1 and MDR3 transcript levels. In a doxorubicin-resistant variant of the LoVo cell line (LoVoDx), MDR3 was expressed at higher levels than MDR1. We also observed high correlations between MDR3 expression and resistance to doxorubicin and paclitaxel. Our results suggest that MDR3 plays an active and important role in drug resistance in the investigated cell lines., (Copyright © 2013 Elsevier Masson SAS. All rights reserved.)

Ovarian cancer is the leading cause of death among gynaecological malignancies. Multiple drug resistance makes cancer cells insensitive to chemotherapy. In this study, we developed six primary ovarian cancer cell lines (W1MR, W1CR, W1DR, W1VR, W1TR, and W1PR) resistant to drugs such as methotrexate, cisplatin, doxorubicin, vincristine, topotecan, and paclitaxel. A chemosensitivity assay MTT test was performed to assess drug cross-resistance. Quantitative real-time polymerase chain reaction and Western blot were also performed to determine mRNA and protein expression of genes involved in chemoresistance. We observed high cross-resistance to doxorubicin, vincristine, and paclitaxel in the cell lines resistant to these agents. We also found a significant correlation between resistance to these drugs and increased expression of P-gp. Two different mechanisms of topotecan resistance were observed in the W1TR and W1PR cell lines. We did not observe any correlation between MRP2 transcript and protein levels. Cell lines resistant to agents used in ovarian cancer treatment remained sensitive to methotrexate. The main mechanisms of drug resistance were due to P-gp expression in the doxorubicin, vincristine, and paclitaxel resistant cell lines and BCRP expression in the topotecan resistant cell line.

The synthesis of several halogenated benzimidazoles substituted in position 2 with trifluoromethyl, pentafluoroethyl and 2-thioethylaminodimethyl group is reported. Antiprotozoal and anticancer activity of series of newly synthesized and previously obtained compounds was studied. All of tested bezimidazoles showed remarkable antiprotozoal activity against Giardia intestinalis, Entamoeba histolytica and Trichomonas vaginalis. Of the studied collection of halogenated benzimidazoles the most anticancer-active was the 5,6-dichloro-2-pentafluoroethyl compound, particularly against breast and prostate cancer cell lines.