In vitro antitumor effects of PI3K inhibitor linperlisib (YY-20394) on acute myeloid leukemia cells

Objective: To investigate the effects of the PI3 K inhibitor, linperlisib (YY20394), on proliferation, Apoptosis, cell cycle and signaling pathways in acute myeloid leukemia (AML) cells.

Methods: The U937 cell cultures were treated with different concentrations of YY20394 to determine the IC50 value by analyzing the cell viability using Cell Counting Kit-8(CCK8). The obtained IC50 value was used for selecting the appropriate concentrations for studies on Apoptosis and cell cycle changes using AO/EB dual fluorescence staining and flow cytometry respectively. The effects of YY20394 on signaling pathways at different concentrations were detected by real-time quantitative PCR (RT-PCR) and Western blotting.

Results: Compared with the control group, YY20394 significantly increased the inhibition rate of proliferation and the Apoptosis rate of AML cells (P < 0.05). Treatment with 5 μM YY20394 led to cell cycle arrest predominantly in the G1phase, while 10um treatment resulted in cell cycle arrest mainly in the G2 phase. Interestingly, YY20394 did not exert its anti-leukemic effects through modulation of the PI3 K/Akt/mTOR Signaling pathway, suggesting that alternative molecular mechanisms may be involved.

Conclusion: YY20394 has a favorable inhibitory effect and significant pro-apoptotic effect on the proliferation of AML cells, which suggests that it has some potential for the treatment of AML.

20394; AML effect mechanism; PI3 K/Akt/mTOR signal path way; YY-.