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|Ref Type||Journal Article|
|Authors||Wang NN, Li ZH, Zhao H, Tao YF, Xu LX, Lu J, Cao L, Du XJ, Sun LC, Zhao WL, Xiao PF, Fang F, Su GH, Li YH, Li G, Li YP, Xu YY, Zhou HT, Wu Y, Jin MF, Liu L, Ni J, Wang J, Hu SY, Zhu XM, Feng X, Pan J|
|Title||Molecular targeting of the oncoprotein PLK1 in pediatric acute myeloid leukemia: RO3280, a novel PLK1 inhibitor, induces apoptosis in leukemia cells.|
|Journal||International journal of molecular sciences|
|Date||2015 Jan 07|
|Abstract Text||Polo-like kinase 1 (PLK1) is highly expressed in many cancers and therefore a biomarker of transformation and potential target for the development of cancer-specific small molecule drugs. RO3280 was recently identified as a novel PLK1 inhibitor; however its therapeutic effects in leukemia treatment are still unknown. We found that the PLK1 protein was highly expressed in leukemia cell lines as well as 73.3% (11/15) of pediatric acute myeloid leukemia (AML) samples. PLK1 mRNA expression was significantly higher in AML samples compared with control samples (82.95 ± 110.28 vs. 6.36 ± 6.35; p < 0.001). Kaplan-Meier survival analysis revealed that shorter survival time correlated with high tumor PLK1 expression (p = 0.002). The 50% inhibitory concentration (IC50) of RO3280 for acute leukemia cells was between 74 and 797 nM. The IC50 of RO3280 in primary acute lymphocytic leukemia (ALL) and AML cells was between 35.49 and 110.76 nM and 52.80 and 147.50 nM, respectively. RO3280 induced apoptosis and cell cycle disorder in leukemia cells. RO3280 treatment regulated several apoptosis-associated genes. The regulation of DCC, CDKN1A, BTK, and SOCS2 was verified by western blot. These results provide insights into the potential use of RO3280 for AML therapy; however, the underlying mechanisms remain to be determined.|
|Molecular Profile||Treatment Approach|
|Gene Name||Source||Synonyms||Protein Domains||Gene Description||Gene Role|
|Drug Name||Trade Name||Synonyms||Drug Classes||Drug Description|
|RO3280||PLK1 Inhibitor 16||RO3280 is an inhibitor of PLK1, which may result in apoptotic activity and inhibition of cell growth (PMID: 25574601, PMID: 31244432).|
|Gene||Variant||Impact||Protein Effect||Variant Description||Associated with drug Resistance|
|Molecular Profile||Indication/Tumor Type||Response Type||Therapy Name||Approval Status||Evidence Type||Efficacy Evidence||References|
|Unknown unknown||acute myeloid leukemia||not applicable||RO3280||Preclinical||Actionable||In a preclinical study, acute myeloid leukemia cells treated with RO3280 in culture demonstrated inhibition of cell growth and apoptotic activity (PMID: 25574601).||25574601|