2020•PubMedRequires access

Inhibitory effect of PI3Kδ inhibitor idelalisib on proliferation of human myeloid leukemia cells and the reversal effect on drug resistance to adriamycin.

Kunlun Li, Pingyong Yi, Hanjia Luo, Jiwei Li, Meng Liu, Min Tang, Weisi Zeng, Shuo Yang, Wei Wang

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Abstract

OBJECTIVES: To investigate the effect of adriamycin (ADM), idelalisib or ADM and their combination on cell proliferation and intracellular concentration of ADM, and to explore the reversal effect of idelalisib on drug resistance to ADM. METHODS: ) and drug resistance index (RI) of ADM to the 2 kinds of cells were measured by methyl thiazolyl tetrazolium (MTT) assay. Non-cytotoxic dose (cell inhibition rate <5%) of idelalisib in the 2 kinds of cells was determined. Then the K562 and k562/ADM cells were divided into the following groups: a K562 cells + ADM group, a K562 cells + ADM + idelalisib group, a K562/ADM cells + ADM group, and a K562/ADM cells + ADM + idelalisib group. The survival rates, the intracellular ATP levels, and the relative concentration of intracellular ADM were detected by MTT method, ATP bioluminescence assay (ATP-BLA) and flow cytometry (FCM), respectively. RESULTS: >0.05). CONCLUSIONS: Idelalisib exerts effect on inhibition of the proliferation in myeloid leukemia K562 and K562/ADM cells, which may partially reverse the drug resistance of K562/ADM cells to ADM. The mechanisms for the effect of idelalisib may be related to increasing the accumulation of ADM and inducing the cell apoptosis in the K562 and K562/ADM cells.

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OBJECTIVES: To investigate the effect of adriamycin (ADM), idelalisib or ADM and their combination on cell proliferation and intracellular concentration of ADM, and to explore the reversal effect of idelalisib on drug resistance to ADM. METHODS: ) and drug resistance index (RI) of ADM to the 2 kinds of cells were measured by methyl thiazolyl tetrazolium (MTT) assay. Non-cytotoxic dose (cell inhibition rate <5%) of idelalisib in the 2 kinds of cells was determined. Then the K562 and k562/ADM cells were divided into the following groups: a K562 cells + ADM group, a K562 cells + ADM + idelalisib group, a K562/ADM cells + ADM group, and a K562/ADM cells + ADM + idelalisib group. The survival rates, the intracellular ATP levels, and the relative concentration of intracellular ADM were detected by MTT method, ATP bioluminescence assay (ATP-BLA) and flow cytometry (FCM), respectively. RESULTS: >0.05). CONCLUSIONS: Idelalisib exerts effect on inhibition of the proliferation in myeloid leukemia K562 and K562/ADM cells, which may partially reverse the drug resistance of K562/ADM cells to ADM. The mechanisms for the effect of idelalisib may be related to increasing the accumulation of ADM and inducing the cell apoptosis in the K562 and K562/ADM cells.

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Available abstract

OBJECTIVES: To investigate the effect of adriamycin (ADM), idelalisib or ADM and their combination on cell proliferation and intracellular concentration of ADM, and to explore the reversal effect of idelalisib on drug resistance to ADM. METHODS: ) and drug resistance index (RI) of ADM to the 2 kinds of cells were measured by methyl thiazolyl tetrazolium (MTT) assay. Non-cytotoxic dose (cell inhibition rate <5%) of idelalisib in the 2 kinds of cells was determined. Then the K562 and k562/ADM cells were divided into the following groups: a K562 cells + ADM group, a K562 cells + ADM + idelalisib group, a K562/ADM cells + ADM group, and a K562/ADM cells + ADM + idelalisib group. The survival rates, the intracellular ATP levels, and the relative concentration of intracellular ADM were detected by MTT method, ATP bioluminescence assay (ATP-BLA) and flow cytometry (FCM), respectively. RESULTS: >0.05). CONCLUSIONS: Idelalisib exerts effect on inhibition of the proliferation in myeloid leukemia K562 and K562/ADM cells, which may partially reverse the drug resistance of K562/ADM cells to ADM. The mechanisms for the effect of idelalisib may be related to increasing the accumulation of ADM and inducing the cell apoptosis in the K562 and K562/ADM cells.

Key concepts: Idelalisib, K562 cells, IC50, Intracellular, Pharmacology, Cytotoxicity, Chemistry, Leukemia

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Inhibitory effect of PI3Kδ inhibitor idelalisib on proliferation of human myeloid leukemia cells and the reversal effect on drug resistance to adriamycin. — Research Paper | ScholarLens