PloS one, 2016-05, Vol.11 (5), p.e0155052-e0155052
2016
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- Autor(en) / Beteiligte
- Titel
- Inhibition of Phospho-S6 Kinase, a Protein Involved in the Compensatory Adaptive Response, Increases the Efficacy of Paclitaxel in Reducing the Viability of Matrix-Attached Ovarian Cancer Cells
- Ist Teil von
- PloS one, 2016-05, Vol.11 (5), p.e0155052-e0155052
- Ort / Verlag
- United States: Public Library of Science
- Erscheinungsjahr
- 2016
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- To identify the proteins involved the compensatory adaptive response to paclitaxel in ovarian cancer cells and to determine whether inhibition of the compensatory adaptive response increases the efficacy of paclitaxel in decreasing the viability of cancer cells. We used a reverse-phase protein array and western blot analysis to identify the proteins involved in the compensatory mechanism induced by paclitaxel in HeyA8 and SKOV3 ovarian cancer cells. We used a cell viability assay to examine whether inhibition of the proteins involved in the compensatory adaptive response influenced the effects of paclitaxel on cancer cell viability. All experiments were performed in three-dimensional cell cultures. Paclitaxel induced the upregulation of pS6 (S240/S244) and pS6 (S235/S236) in HeyA8 and SKOV3 cells, and pPRAS40 (T246) in HeyA8 cells. BX795 and CCT128930 were chosen as inhibitors of pS6 (S240/S244), pS6 (S235/S236), and pPRAS40 (T246). BX795 and CCT128930 decreased pS6 (S240/S244) and pS6 (S235/S236) expression in HeyA8 and SKOV3 cells. However, pPRAS40 (T246) expression was inhibited only by BX795 and not by CCT128930 in HeyA8 cells. Compared with paclitaxel alone, addition of BX795 or CCT128930 to paclitaxel was more effective in decreasing the viability of HeyA8 and SKOV3 cells. Addition of BX795 or CCT128930 to inhibit pS6 (S240/S244) or pS6 (S235/S236) restricted the compensatory adaptive response to paclitaxel in HeyA8 and SKOV3 cells. These inhibitors increased the efficacy of paclitaxel in reducing cancer cell viability.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 1932-6203eISSN: 1932-6203DOI: 10.1371/journal.pone.0155052Titel-ID: cdi_plos_journals_1787084554
- Format
- –
- Schlagworte
- Antineoplastic Agents, Phytogenic - pharmacology, Biology and Life Sciences, Cancer, Cancer therapies, Cell culture, Cell cycle, Cell growth, Cell Line, Tumor, Cell Survival - drug effects, Chemotherapy, Clinical medicine, Complications and side effects, Dosage and administration, Drug resistance, Drug therapy, Effectiveness, Female, Genetic aspects, Growth factors, Gynecology, Humans, Inhibition, Inhibitors, Kinases, Medical research, Medicine, Medicine and Health Sciences, Mutation, Obstetrics, Ovarian cancer, Ovarian carcinoma, Ovarian Neoplasms - drug therapy, Ovarian Neoplasms - metabolism, Paclitaxel, Paclitaxel - pharmacology, Physiological aspects, Protein arrays, Protein kinases, Proteins, Research and Analysis Methods, Ribosomal Protein S6 Kinases - metabolism, Signal transduction, Signal Transduction - drug effects, Up-Regulation - drug effects