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顺铂与帕博西尼联合用药通过热休克蛋白90对肝癌细胞中的PTEN-AKT信号通路产生不同调节作用。

Cisplatin palbociclib combination differentially modulates PTEN AKT signaling via Hsp90 in hepatocellular carcinoma cells.

作者信息

Sleem Hameis M, Ali Aya A, Ramadan Eman

机构信息

Department of Pharmacology and Biochemistry, Faculty of Pharmacy, The British University in Egypt, El Sherouk City, Egypt.

Drug Research and Development Group (DRD), Health Research Center of Excellence, The British University in Egypt, El Sherouk City, Egypt.

出版信息

Sci Rep. 2025 Jun 2;15(1):19319. doi: 10.1038/s41598-025-04008-1.

DOI:10.1038/s41598-025-04008-1
PMID:40456804
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12130490/
Abstract

Hepatocellular carcinoma (HCC) presents a significant global health challenge, marked by high mortality and recurrence. This study investigated the synergistic potential of cisplatin and palbociclib (C + P) against HCC cell lines. RT-qPCR revealed that C + P significantly downregulated HCC-related genes, including Hsp90, β-catenin, and components of the PI3K/AKT/mTOR pathway, compared to cisplatin alone and controls. Western blotting confirmed a reduction in phosphorylated AKT (P-AKT) with palbociclib and C + P, while PTEN, a tumor suppressor, was upregulated in the C + P group. Annexin V-FITC assays demonstrated a substantial increase in apoptosis in palbociclib and C + P treated cells. Cell cycle analysis indicated S and G0-G1 phase arrest with C + P, suggesting a combined cytotoxic effect. Scratch wound assays showed that both palbociclib and C + P significantly inhibited cell migration compared to cisplatin and controls. These findings suggest a promising synergistic effect of C + P in overcoming cisplatin resistance in HCC. However, further research is needed to fully elucidate the complex interactions between these drugs.

摘要

肝细胞癌（HCC）是一项重大的全球健康挑战，其特点是高死亡率和高复发率。本研究调查了顺铂和帕博西尼（C+P）联合使用对肝癌细胞系的协同作用潜力。逆转录定量聚合酶链反应（RT-qPCR）显示，与单独使用顺铂及对照组相比，C+P显著下调了包括热休克蛋白90（Hsp90）、β-连环蛋白以及磷脂酰肌醇-3-激酶/蛋白激酶B/哺乳动物雷帕霉素靶蛋白（PI3K/AKT/mTOR）信号通路相关成分在内的肝癌相关基因。蛋白质免疫印迹法证实，帕博西尼以及C+P组中磷酸化蛋白激酶B（P-AKT）水平降低，而肿瘤抑制因子磷酸酶和张力蛋白同源物（PTEN）在C+P组中上调。膜联蛋白V-异硫氰酸荧光素（Annexin V-FITC）检测表明，经帕博西尼和C+P处理的细胞凋亡显著增加。细胞周期分析表明，C+P组出现S期和G0-G1期阻滞，提示存在联合细胞毒性作用。划痕试验显示，与顺铂及对照组相比，帕博西尼和C+P均显著抑制细胞迁移。这些发现表明，C+P在克服肝癌顺铂耐药方面具有良好的协同作用。然而，需要进一步研究以充分阐明这些药物之间的复杂相互作用。

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本文引用的文献

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