INNO-406 inhibit the growth of chronic myeloid leukemia and promote its apoptosis via targeting PTEN
Chronic myeloid leukemia (CML) is a myeloproliferative neoplasm. INNO-406 is a novel tyrosine kinase inhibitor (TKI) that possess specific Lyn kinase inhibitory activity with no or limited activity against other sarcoma (Src) family member kinases. The present study aimed to confirm the anti-tumor effect of INNO-406 on CML cells, and elucidate the molecular mechanism underlying its effect. Methods The cell proliferation and apoptosis were detected by MTT, western blot and flow cytometry
... w cytometry respectively. Results As suggested by the findings, INNO-406 significantly inhibited the proliferation and induced apoptosis of CML cells. In addition, INNO-406 promoted the expression level of PETN. Rescue experiment revealed that PTEN knockdown reversed the effect of INNO-406 which indicated the correlation between INNO-406 and PTEN. Further study determined that PTEN inhibited the phosphorylation of AKT and 4EBP1 and subsequently altered the expression of apoptotic protein expressions including bax, cytochrome c (cyto-c), cleaved caspase3 and bcl-2. In vivo study further confirmed that INNO-406 inhibited the growth of CML cells in vivo by targeting PTEN. Conclusion Based on the above findings, this work extended our understanding of INNO-406 in the chemotherapy of CML and its molecular mechanism.