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Additionally, PHLPP1 inhibition significantly reduced HG-induced apoptosis and restored PI3K/AKT/mTOR pathway activity in H9c2 cells. Furthermore, pretreatment with LY294002, an inhibitor of PI3K/Akt/mTOR pathway, abolished the anti-apoptotic effect of PHLPP1 inhibition. CONCLUSION Our study indicated that PHLPP1 inhibition alleviated cardiac dysfunction via activating the PI3K/Akt/mTOR signalling pathway in DCM. Therefore, PHLPP1 may be a novel therapeutic target for human DCM. © 2020 The Authors. Journal of Cellular and Molecular Medici