ZHENG Shuwen,HUANG Huijing,CHEN Guo, et al. The inhibitory mechanism of a novel small molecular compound cyy-287 combined with CDK inhibitor roscovitine in SBC-2 cell growth[J]. JOURNAL OF WEZHOU MEDICAL UNIVERSITY, 2023, 53(2): 109-114.
Abstract：Objective: To explore the inhibitory effect of a new small molecule compound cyy-287,combined with cyclin dependent kinase (CDK) inhibitor roscovitine on the small cell lung cancer cell line SBC-2 and its mechanism. Methods: SBC-2 cells in logarithmic growth period were taken. The IC50 values of cyy-287 and the combination index (CI) of cyy-287 and roscovitine were detected by MTS. Experimental groups of cyy-287 in combination with roscovitine for antitumor activity studies were as follows: DMSO (control) group;roscovitine (20 μmol/L) group; cyy-287 (1.5 μmol/L) group and cyy-287+roscovitine group. The proliferation of tumor cells after drug treatment in each group was detected by clone formation experiment. The distribution of cell cycle and the proportion of apoptosis were measured by flow cytometry. The protein expression level of CLPARP and the phosphorylation level of AKT in each treatment group were detected by Western blot. Results:The IC50 of cyy-287 in SBC-2 was (1.77±0.10)μmol/L. The CI of cyy-287 and roscovitine was less than 1, which means that cyy-287 combined with rescovitine has synergistic effect on SBC-2 cells. Compared with cyy-287 alone treatment group, a combination of the two drugs could significantly inhibit the growth and clonogenesis of SBC-2 cells (P<0.001), and the proportion of apoptotic cells increased significantly (P<0.001). The protein expression level of apoptosis related CL-PARP increased significantly, and the expression level of P-AKT decreased (P<0.05). Conclusion: The combination of cyy-287 and roscovitine has a synergistic antitumor effect,which can effectively inhibit the growth of SBC-2 cells and induced their apoptosis. Its underlying mechanism is mainly suppressing the cell survival by inhibiting the phosphorylation of AKT.
