Palbociclib inhibits the progression of head and neck cancer and improves the Cetuximab response under specific condition in vitro and in vivo.

Autor: Li R; Department of Radiation Oncology, Eye & ENT Hospital of Fudan University, 83 Fenyang Road, Shanghai, 200031, China., Wang Q; Department of Plastic Surgery, Jiahui International Hospital, Jiahui Health, Shanghai, 200031, China., Zhao Y; Department of Radiation Oncology, Eye & ENT Hospital of Fudan University, 83 Fenyang Road, Shanghai, 200031, China., Zhu Y; Department of Radiation Oncology, Eye & ENT Hospital of Fudan University, 83 Fenyang Road, Shanghai, 200031, China. zhuyi1113@hotmail.com., Wang X; Department of Radiation Oncology, Eye & ENT Hospital of Fudan University, 83 Fenyang Road, Shanghai, 200031, China. xiaoshen.wang@fdeent.org.
Jazyk: angličtina
Zdroj: Molecular biology reports [Mol Biol Rep] 2024 Mar 27; Vol. 51 (1), pp. 455. Date of Electronic Publication: 2024 Mar 27.
DOI: 10.1007/s11033-024-09423-7
Abstrakt: Background: In head and neck squamous cell carcinoma (HNSCC) with human papillomavirus (HPV)-negative, deregulation of cell cycle is partly due to inactivation of p16INK4 and overexpression of cyclin D1. Here we investigated the in vitro and in vivo effects of the CDK4/6 inhibitor Palbociclib alone or combined with EGFR inhibitor Cetuximab in HNSCC.
Methods and Results: CCK-8, soft agar assay, colony formation assay, wound healing assay and transwell assay, β-galactosidase assay, western blotting, and cell-derived xenografts were used to investigated the in vitro and in vivo activity of drugs. Cell viability and colony formation decreased in a dose-dependent manner in Tu686, AMC-HN8, and Fadu cells under Palbociclib treatment. Palbociclib remarkably inhibited migration, invasion and the expression MMP-9 in HNSCC cells. Palbociclib also induced senescence. Palbociclib caused the dephosphorylation of RB but increased the cyclin D1 level in a dose-dependent manner. Moreover, combination with Cetuximab could significantly prevent the induction of cyclin D1 and activation of EGFR signals from Palbociclib treatment. Nevertheless, only within the range of certain concentrations, a synergistic inhibitory effect on cell growth was observed when combined with Palbociclib and Cetuximab. Although the synergistic effect in Palbociclib/Cetuximab combined therapy was comparable to that in traditional chemotherapeutic regimens (cisplatin/Cetuximab) in Fadu tumor xenograft, the combination therapy was less active than Cetuximab monotherapy in Tu686 tumor xenograft.
Conclusion: In HPV-negative HNSCC, CDK4/6 inhibitor shows promising anti-tumor effects, which exhibits a synergistic effect when combined with EGFR inhibitor only in specific drug concentration and mouse model.
(© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)
Databáze: MEDLINE
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