LKB1 regulates the PTEN/PI3K/AKT pathway to induce multiple myeloma cell apoptosis
[Objective]To investigate the potential mechanism of LKB1-induced apoptosis in multiple myeloma cells.[Meth-od]LKB1 knockout cell line was constructed,and the proliferation level,apoptosis level and PTEN/PI3K/AKT path-related protein expression level of multiple myeloma cells RPMI 8266 and U266 with and without LKB1 knockout were compared.Ap-optosis levels were detected after overexpression of LKB1 wild type(LKBI WT)or LKB1 active mutant(LKB1 K78M)in RPMI 8266 and U266 LKB1 knockout cell lines.After treatment with PTEN inhibitor and activator,PI3K inhibitor and activator,AKT inhibitor and activator,the apoptotic level of multiple myeloma cell lines with LKB1 knockout was detected.[Result]After LKB1 knockout,the proliferation level of multiple myeloma cells RPMI 8266 and U266 increased(2.67±0.10 vs 3.46±0.08,P＜0.05),and the apoptosis level decreased(15.74％±3.17％vs 6.68％±1.34％,P＜0.05).Compared with the LKB1 wild type,the proliferation level of LKB1 K78M increased(2.15±0.10 vs 3.51±0.08,P＜0.05),and the apoptosis level de-creased(36.98％±3.36％vs 6.05％±1.32％,P＜0.05).After LKB1 knockout,the expression level of p-AKT and p-PI3K in multiple myeloma cells RPMI 8266 and U266 increased,while the level of PTEN decreased,while the level of AKT and PI3K did not change significantly.PTEN activator,PI3K inhibitor and AKT inhibitor could restore the proliferation level and ap-optosis level of RPMI 8266 and U266 LKB1 knockout cells to the state without LKB1 knockout(6.88％±1.42％vs 15.39％±3.21％,P＜0.05).[Conclusion]LKB1 induces multiple myeloma cell apoptosis by regulating the PTEN/PI3K/AKT pathway.
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