Abstract: Objective The objective of this study was to investigate the effect and mechanism of novel multi-target kinase inhibitor ON123300 on the proliferation,cycle and apoptosis of ER-positive and HER2-negative human breast cancer MCF-7 cells.Methods MCF-7 cells in logarithmic growth phase were treated with ON123300 or palbocilib for 48 h.DMSO was used as the control.The cellular morphology of MCF-7 cells was observed by optical microscope and the cell proliferation was measured by CCK8 assay.Flow cytometry(FCM)was used to detect cell cycle and apoptosis.Western blot was used to examine the expression of cyclinD1,CDK4,pRb1,survivin and PI3K protein in MCF-7 cells.Results No cell morphological changes of MCF-7 cells were observed in the control group.In the palbocilib group,MCF-7 cells showed slight inhibition of cell proliferation and a small amount of cell shedding.In the ON123300 group,cell proliferation was significantly inhibited and cell morphology changes,showing a shedding phenomenon.The inhibitory rate increased with increasing drug concentration,showing a dose-dependent manner.The cells in the ON123300 treated group were significantly arrested at the G1/S phase of cell cyde and were associated with increased apoptosis,with a statistically significant difference(P＜0.05).The protein expression of cyclinD1,CDK4,pRb1,survivin and PI3K in the ON123300-treated group were obviously reduced than those in the control group(P＜0.05).Conclusion ON123300 can significantly inhibit proliferation,promote cell cycle arrest and apoptosis of MCF-7 cells.The mechanism may be related to the inhibition of survivin/cyclinD1/CDK4/Rb1/PI3K signaling pathways.

Key words: ON123300, Breast cancer, Cell cycle