Sensitivity to anticancer agents and resistance mechanisms in clear cell carcinoma of the ovary

Autor: Hiroaki Itamochi, Naoki Terakawa, Takahiro Iba, Yasunobu Kanamori, Junzo Kigawa, Habiba Sultana, Ryoji Akeshima, Shunji Kamazawa
Rok vydání: 2002
Předmět:
Cancer Research
Tetrazolium Salts
chemistry.chemical_compound
Resistance mechanism
Gene expression
Tumor Cells
Cultured
Coloring Agents
Etoposide
Clear cell carcinoma
Ovarian Neoplasms
Antibiotics
Antineoplastic
Reverse Transcriptase Polymerase Chain Reaction
Glutathione
Multidrug Resistance-Associated Protein 2
Oncology
Paclitaxel
DNA Topoisomerases
Type I
Area Under Curve
Female
Multidrug Resistance-Associated Proteins
medicine.drug
Ribosomal Proteins
Saccharomyces cerevisiae Proteins
Mitomycin
Antineoplastic Agents
Biology
Irinotecan
Article
Mitochondrial Proteins
Inhibitory Concentration 50
Ovarian cancer
medicine
Humans
Chemotherapy
ATP Binding Cassette Transporter
Subfamily B
Member 1
RNA
Messenger
Cisplatin
Dose-Response Relationship
Drug
Topoisomerase
Molecular biology
Antineoplastic Agents
Phytogenic
Thiazoles
chemistry
Cell culture
Drug Resistance
Neoplasm
Immunology
biology.protein
Camptothecin
Adenocarcinoma
Clear Cell
Zdroj: Japanese Journal of Cancer Research : Gann
ISSN: 0910-5050
Popis: We conducted the present study to determine the chemoresistance mechanisms in clear cell carcinoma of the ovary (CCC). Five human CCC cell lines (HAC-2, RMG-1, RMG-II, KK, and KOC-7c) were used in this study. The sensitivity of the cells to the anticancer agents was determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and we assessed drug sensitivity by calculating assay area under the curve (AUC) for each agent. The expression of multi-drug resistance genes (MDR-1, MRP-1, MRP-2) was detected by reverse transcription-polymerase chain reaction (RT-PCR). Glutathione (GSH) concentration was measured by an enzymatic assay. Topoisomerase (topo) I activity was assayed in terms of relaxation of supercoiled plasmid substrate DNA. The IC 5 0 to anticancer agents ranged widely. The assay AUC indicated that 3 of 5 cell lines (RMG-I, RMG-II, and KK) were sensitive to paclitaxel (PTX), 3 (HAC-2, RMG-I, and RMG-II) were sensitive to 7-ethyl-10-hydroxycamptothecin (SN-38), which is an active metabolite of camptothecin (CPT-11), and only one (HAC-2) was sensitive to cisplatin (CDDP). All cell lines were resistant to mitomycin-C (MMC) and etoposide (VP-16). The MRP-1 gene was detected in all cell lines. Only one cell line showed both MRP-2 and MDR-1 gene expression. Except for HAC-2 cells, expression of MRP genes was related to CDDP resistance, and MDR-I gene expression was associated with PTX resistance. GSH concentrations increased after exposure to CDDP or MMC in all cell lines. There was a significant correlation between topo-I enzymatic activity and the response to SN-38. The present study revealed several resistance mechanisms in CCC and the results suggested that PTX and CPT-11 might be effective agents to treat CCC.
Databáze: OpenAIRE
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