PloS one, 2014-12, Vol.9 (12), p.e115708-e115708
2014
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- Autor(en) / Beteiligte
- Titel
- Citrate synthase expression affects tumor phenotype and drug resistance in human ovarian carcinoma
- Ist Teil von
- PloS one, 2014-12, Vol.9 (12), p.e115708-e115708
- Ort / Verlag
- United States: Public Library of Science
- Erscheinungsjahr
- 2014
- Quelle
- Free E-Journal (出版社公開部分のみ）
- Beschreibungen/Notizen
- Citrate synthase (CS), one of the key enzymes in the tricarboxylic acid (TCA) cycle, catalyzes the reaction between oxaloacetic acid and acetyl coenzyme A to generate citrate. Increased CS has been observed in pancreatic cancer. In this study, we found higher CS expression in malignant ovarian tumors and ovarian cancer cell lines compared to benign ovarian tumors and normal human ovarian surface epithelium, respectively. CS knockdown by RNAi could result in the reduction of cell proliferation, and inhibition of invasion and migration of ovarian cancer cells in vitro. The drug resistance was also inhibited possibly through an excision repair cross complementing 1 (ERCC1)-dependent mechanism. Finally, upon CS knockdown we observed significant increase expression of multiple genes, including ISG15, IRF7, CASP7, and DDX58 in SKOV3 and A2780 cells by microarray analysis and real-time PCR. Taken together, these results suggested that CS might represent a potential therapeutic target for ovarian carcinoma.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 1932-6203eISSN: 1932-6203DOI: 10.1371/journal.pone.0115708Titel-ID: cdi_plos_journals_1640859530
- Format
- –
- Schlagworte
- Acids, Adenosine Triphosphate - metabolism, AMP-Activated Protein Kinases - metabolism, Antineoplastic Agents - pharmacology, Apoptosis, Apoptosis - drug effects, Autophagy, Breast cancer, Cancer, Cancer therapies, Carcinoma, Carcinoma, Ovarian Epithelial, Cell growth, Cell Line, Tumor, Cell migration, Cell Movement - drug effects, Cell proliferation, Cell Proliferation - drug effects, Chemotherapy, Cisplatin - pharmacology, Citrate (si)-Synthase - genetics, Citrate (si)-Synthase - metabolism, Citrate synthase, Coenzyme A, Comparative analysis, Deoxyribonucleic acid, DNA, DNA microarrays, DNA repair, Drug resistance, Drug Resistance - drug effects, Drug therapy, Enzymes, Epithelium, ERCC1 protein, Female, Gene expression, Gene Knockdown Techniques, Genes, Gynecology, Health aspects, Hospitals, Humans, Interferon regulatory factor 7, Kinases, Laboratories, Lung cancer, Medicine, Medicine and Health Sciences, Mortality, Neoplasm Invasiveness, Neoplasms, Glandular and Epithelial - metabolism, Neoplasms, Glandular and Epithelial - pathology, Obstetrics, Oncology, Ovarian cancer, Ovarian carcinoma, Ovarian Neoplasms - metabolism, Ovarian Neoplasms - pathology, Oxaloacetic acid, p38 Mitogen-Activated Protein Kinases - metabolism, Pancreatic cancer, Phenotype, RNA, Small Interfering - pharmacology, RNA-mediated interference, Tricarboxylic acid cycle, Tumor cell lines, Tumors