The international journal of biochemistry & cell biology, 2019-11, Vol.116, p.105615-105615, Article 105615
2019
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Details
- Autor(en) / Beteiligte
- Titel
- Inhibition of PI3K pathway using BKM120 intensified the chemo-sensitivity of breast cancer cells to arsenic trioxide (ATO)
- Ist Teil von
- The international journal of biochemistry & cell biology, 2019-11, Vol.116, p.105615-105615, Article 105615
- Ort / Verlag
- Netherlands: Elsevier Ltd
- Erscheinungsjahr
- 2019
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- Although conventional therapeutic approaches have brought remarkable advantages for the treatment of breast cancer (BC), drug-resistance still remains as a leading cause of tumor recurrence in this malignancy. In the present study, we designed experiments to evaluate the therapeutic value of PI3K inhibition in combination with Arsenic trioxide (ATO) in MCF-7 cells. The results of our study manifested that BKM120 sensitized MCF-7 cells to the lower concentrations of ATO. The significant anti-cancer effect of PI3K inhibition became even more evident when we found that BKM120, either as a single agent or in combination with ATO, reduced clonogenic ability of anoikis-resistant stem-like MCF-7 cells. Our findings also showed that BKM120 augmented ATO-induced anti-proliferative effects through inducing G1 arrest and reducing the incorporation of BrdU into the synthesized DNA of drugs-treated cells, which was coupled with c-Myc-mediated suppression of hTERT expression. Moreover, we found that in the presence of PI3K inhibitor, ATO is able to more profoundly induce apoptosis in MCF-7 cells, as revealed by the increment in the percentage of haplodiploid sub-G1 cells and the externalization of phosphatidylserine. Real-time PCR analysis also revealed that probably down-regulation of survivin coupled with up-regulation of forkhead family transcription factors is responsible for the enhancive effect of drugs in this cell line. Conclusively, this study shed lights on the effect of PI3K inhibition in chemo-sensitivity of MCF-7 cells, disclosing that combination of BKM120 and ATO could be a promising therapeutic approach in BC.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 1357-2725eISSN: 1878-5875DOI: 10.1016/j.biocel.2019.105615Titel-ID: cdi_proquest_miscellaneous_2295486727
- Format
- –
- Schlagworte
- Aminopyridines - pharmacology, Anoikis - drug effects, Anoikis - genetics, Antineoplastic Agents - pharmacology, Arsenic trioxide (ATO), Arsenic Trioxide - pharmacology, BKM120 (Buparlisib), Breast cancer, CAL-101 (Idelalisib), Cell Line, Cell Proliferation - drug effects, DNA-Binding Proteins - genetics, DNA-Binding Proteins - metabolism, Drug Combinations, Drug Synergism, Epithelial Cells - drug effects, Epithelial Cells - metabolism, Epithelial Cells - pathology, Female, Forkhead Transcription Factors - agonists, Forkhead Transcription Factors - genetics, Forkhead Transcription Factors - metabolism, G1 Phase Cell Cycle Checkpoints - drug effects, G1 Phase Cell Cycle Checkpoints - genetics, Gene Expression Regulation, Neoplastic, Humans, MCF-7 Cells, Morpholines - pharmacology, Phosphatidylinositol 3-Kinases - genetics, Phosphatidylinositol 3-Kinases - metabolism, Phosphatidylserines - metabolism, PI3K signaling pathway, Signal Transduction, Survivin - antagonists & inhibitors, Survivin - genetics, Survivin - metabolism, Telomerase - antagonists & inhibitors, Telomerase - genetics, Telomerase - metabolism, Transcription Factors - genetics, Transcription Factors - metabolism