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

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Abstract

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.

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Data availability

The data that support the conclusions of this study are obtained from the corresponding author upon reasonable request.

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Funding

This study was supported by the Medical Guidance Project of the Shanghai Science and Technology Commission [number 21Y11900300] and the National Key R&D Program of China [number 2020YFE0205500].

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Author notes

  1. Ruichen Li and Qi Wang authors contributed equally to this work.

Authors and Affiliations

  1. Department of Radiation Oncology, Eye & ENT Hospital of Fudan University, 83 Fenyang Road, Shanghai, 200031, China

    Ruichen Li, Yang Zhao, Yi Zhu & Xiaoshen Wang

  2. Department of Plastic Surgery, Jiahui International Hospital, Jiahui Health, Shanghai, 200031, China

    Qi Wang

Authors
  1. Ruichen Li
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  2. Qi Wang
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  3. Yang Zhao
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  4. Yi Zhu
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Contributions

Ruichen Li: Conceptualization, Methodology, Software, Formal analysis, Investigation, Visualization, Writing-Original Draft; Qi Wang: Methodology, Software, Formal analysis, Validation, Visualization, Writing-Original Draft; Yang Zhao: Investigation, Formal analysis; Yi Zhu: Conceptualization, Methodology, Supervision, Writing-Review & Editing; Xiaoshen Wang: Conceptualization, Supervision, Project administration, Funding acquisition, Writing-Review & Editing.

Corresponding authors

Correspondence to Yi Zhu or Xiaoshen Wang.

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Ethical approval

Animal studies were performed on the basis of the International Animal Care and Use Committee-approved protocol (IACUC). The research was approved by the Ethics Committee of the Eye & ENT Hospital of Fudan University (approval numbers: 2019062-1).

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The authors declare no potential conflicts of interest.

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Li, R., Wang, Q., Zhao, Y. et al. Palbociclib inhibits the progression of head and neck cancer and improves the Cetuximab response under specific condition in vitro and in vivo. Mol Biol Rep 51, 455 (2024). https://doi.org/10.1007/s11033-024-09423-7

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