Synergistic effects of GS-1101 and Doxorubicin in acute lymphoblastic leukemia cell line
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 effec...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Mazandaran University of Medical Sciences
2017-10-01
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| Series: | Journal of Mazandaran University of Medical Sciences |
| Subjects: | |
| Online Access: | http://jmums.mazums.ac.ir/article-1-9337-en.html |
| Summary: | 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. |
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| ISSN: | 1735-9260 1735-9279 |