ArticleOncotarget2017
Antiproliferative effect of ZSTK474 alone or in combination with chemotherapeutic drugs on HL60 and HL60/ADR cells.
Article in Oncotarget, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
8 citing papers in PubMed, 13 citations in OpenAlex.
- BKM120 sensitizes glioblastoma to the PARP inhibitor rucaparib by suppressing homologous recombination repair.Cell death & disease · 2021Article
- Combination of coumarin and doxorubicin induces drug-resistant acute myeloid leukemia cell death.Heliyon · 2021Article
- Reversal of TGF-β-induced epithelial-mesenchymal transition in hepatocellular carcinoma by sorafenib, a VEGFR-2 and Raf kinase inhibitor.Current research in pharmacology and drug discovery · 2021Article
- Multifaceted anti-colorectal tumor effect of digoxin on HCT8 and SW620 cellsGastroenterology report · 2020Article
- A cell-based high-throughput screen identifies inhibitors that overcome P-glycoprotein (Pgp)-mediated multidrug resistance.PloS one · 2020Article
- Co-targeting PI3K/Akt and MAPK/ERK pathways leads to an enhanced antitumor effect on human hypopharyngeal squamous cell carcinoma.Journal of cancer research and clinical oncology · 2019Article
- Retracted Article: LncRNA ZEB2-AS1 regulates the drug resistance of acute myeloid leukemiaRSC advances · 2019Article
- Targeting signaling and apoptotic pathways involved in chemotherapeutic drug-resistance of hematopoietic cells.Oncotarget · 2017Article
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Authors and funding
10 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
While chemotherapy remains to be one of the main approaches in the clinical treatment of acute myeloid leukemia (AML), multidrug resistance (MDR) has become a serious problem which limits the therapeutic efficacy. The important roles of the PI3K/Akt pathway in modulating cell proliferation and MDR suggest that PI3K inhibitor might be effective for treatment of AML. In the present study, the antiproliferative effects of PI3K inhibitor ZSTK474 on AML cell HL60 and the adriamycin (ADR)-resistant HL60/ADR cells were investigated. Our data indicated that ZSTK474 exhibited potent antiproliferative activity, induced G1 cell cycle arrest, but no obvious apoptosis in both cell lines. Moreover, ZSTK474 affected the protein levels of cell-cycle-related molecules including increased p27, decreased cyclin D1 and phosphorylated Rb in dose-dependent manner. The proteins downstream of PI3K including phosphorylated PDK1, Akt and GSK-3β were reduced in a dose-dependent manner after ZSTK474 treatment. ZSTK474 reversed ADR resistance, increased the intracellular accumulation of ADR, and reduced the expression and function of multidrug resistance (MDR) proteins including both P-gp and MRP1 in HL60/ADR cells. The combination of ZSTK474 and chemotherapeutic drugs cytarabine or vincristine led to a synergistic effect in HL60 and HL60/ADR cells. In conclusion, ZSTK474 showed potent antiproliferative effect on HL60 and HL60/ADR cells; combination with cytarabine or vincristine resulted in synergistic effect. Our results suggest ZSTK474 has the potential to be applied in the treatment of AML patients, while further evidences particularly those about in vivo efficacy are needed.
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