Qingsong Chen

Pan-Cdk inhibitor ZK304709 suppresses Cdc20 expression and potentiates the anticancer activity of apcin in HeLa cervical cancer cells

Abstract Cell division cycle 20 homologue (Cdc20), a key regulator of the anaphase-promoting complex/cyclosome (APC/C), is frequently overexpressed in human cancers and represents a promising therapeutic target. However, monotherapy targeting Cdc20 has shown limited efficacy, partly due to compensatory activation of cyclin-dependent kinase 1 (Cdk1). In this study, we investigated the combinatorial potential of the pan-Cdk inhibitor ZK304709 with the Cdc20 inhibitor apcin in HeLa cervical cancer cells. Transcriptomic analysis revealed that both CDC20 and CDK1 are upregulated in cervical cancer tissues. Mechanistically, apcin treatment induced cyclin B1 accumulation and enhanced Cdk1 phosphorylation at Thr161, suggesting feedback activation. In contrast, ZK304709 reduced p -Cdk1(T161) levels and suppressed Cdc20 expression at both protein and mRNA levels. Functionally, the combination of apcin and ZK304709 synergistically inhibited cell proliferation and induced G2/M phase arrest in HeLa cells. These findings demonstrate that dual inhibition of Cdk1 and Cdc20 disrupts compensatory signalling pathways and enhances antitumour efficacy in HeLa cells, providing a rational strategy for combination therapy in cervical cancer.

Novel prognostic nomograms in cervical cancer based on analysis of 1075 patients

AbstractObjectiveTo explore the factors affecting the prognosis of cervical cancer (CC), and to construct and evaluate predictive nomograms to guide individualized clinical treatment.MethodsThe clinicopathological and follow‐up data of CC patients from June 2013 to December 2019 in Sun Yat‐sen Memorial Hospital of Sun Yat‐sen University were retrospectively analyzed. Log‐rank test was used for univariate survival analysis, and Cox multivariate regression was used to identify independent prognostic factors, based on which nomogram models were established and evaluated in multiple aspects.ResultsPatients were randomly assigned into the training (n = 746) and validation sets (n = 329). Survival analysis of the training set identified cervical myometrial invasion, parametrial involvement, and malignant tumor history as prognosticators of postoperative DFS and pathological type, cervical myometrial invasion, and history of STD for OS. C‐index was 0.799 and 0.839 for the nomograms for DFS and OS, respectively. Calibration curves and Brier scores also indicated high performance. Importantly, decision curve analysis suggested great clinical applicability of these nomograms.ConclusionsIn this study, we analyzed a cohort of 1075 CC patients and identified DFS‐ or OS‐associated clinicohistologic characteristics. Two nomograms were subsequently constructed for DFS and OS prognostication, respectively, and showed high performance in terms of discrimination, calibration, and clinical applicability. These models may facilitate individualized treatment and patient selection for clinical trials. Future investigations with larger cohorts and prospective designs are warranted for validating these prognostic models.