Volume 27, Issue 153 (10-2017)
J Mazandaran Univ Med Sci 2017, 27(153): 28-38 |
Back to browse issues page
Download citation:
BibTeX | RIS | EndNote | Medlars | ProCite | Reference Manager | RefWorks
Send citation to:
BibTeX | RIS | EndNote | Medlars | ProCite | Reference Manager | RefWorks
Send citation to:
Safaroghli-Azar A, Sadreazami P, Bahmani F, Bashash D. Synergistic effects of GS-1101 and Doxorubicin in acute lymphoblastic leukemia cell line. J Mazandaran Univ Med Sci 2017; 27 (153) :28-38
URL: http://jmums.mazums.ac.ir/article-1-9337-en.html
URL: http://jmums.mazums.ac.ir/article-1-9337-en.html
Abstract: (5454 Views)
Background and purpose: Interest into targeting PI3K in cancer has increased by the recent disclosure that aberrant activity of PI3K/Akt signaling pathway is associated with disease recurrence and poor outcome in different malignancies. The aim of this study was to investigate the potentiating effect of PI3K inhibitor, GS-1101 on doxorubicin-induced cell death in acute lymphoblastic leukemia-derived, Nalm-6 cells.
Materials and methods: In this experimental study, to evaluate whether abrogating PI3K/Akt pathway using GS-1101 could enhance cytotoxic effect of doxorubicin in acute lymphoblastic leukemia, Nalm-6 pre-B ALL cells were subjected to combination treatment and subsequent cell viability. Then cell count, metabolic activity, and transcriptional alteration of apoptosis-related target genes were investigated using Trypan blue exlussion, MTT and Rq-PCR analysis, respectively.
Results: Our data delineated that GS-1101 augments doxorubicin-induced cytotoxic and its anti-proliferative effect, as evidenced by the decreased cell survival, cellular metabolic activity, and reduction in the number of inhibitor-treated viable cells. Moreover, real-time PCR analysis revealed that induction of cell death by the drug combination was associated with increased Bax transcriptional activity (P≤0.01) followed by the elevated molecular ratio of Bax/Bcl-2 (P≤0.001).
Conclusion: This study suggested that abrogation of the PI3K pathway using GS-1101 could potentiate doxorubicin-induced anti-leukemic activity.
Materials and methods: In this experimental study, to evaluate whether abrogating PI3K/Akt pathway using GS-1101 could enhance cytotoxic effect of doxorubicin in acute lymphoblastic leukemia, Nalm-6 pre-B ALL cells were subjected to combination treatment and subsequent cell viability. Then cell count, metabolic activity, and transcriptional alteration of apoptosis-related target genes were investigated using Trypan blue exlussion, MTT and Rq-PCR analysis, respectively.
Results: Our data delineated that GS-1101 augments doxorubicin-induced cytotoxic and its anti-proliferative effect, as evidenced by the decreased cell survival, cellular metabolic activity, and reduction in the number of inhibitor-treated viable cells. Moreover, real-time PCR analysis revealed that induction of cell death by the drug combination was associated with increased Bax transcriptional activity (P≤0.01) followed by the elevated molecular ratio of Bax/Bcl-2 (P≤0.001).
Conclusion: This study suggested that abrogation of the PI3K pathway using GS-1101 could potentiate doxorubicin-induced anti-leukemic activity.
Type of Study: Research(Original) |
Subject:
Hematology and Oncology
Send email to the article author
| Rights and permissions | |
 |
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License. |
Articles Copyright © The Author(s). Owned by Mazandaran University of Medical Sciences.
Contact Us
Address: Journal Office, Building No. 2, Mazandaran University of Medical Sciences, Moallem Square, Sari.Tel: +98 (011)34484874 Postal code: 48175-866 E-Mail: jmums@mazums.ac.ir Telefax: +98 (011)33262679
