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Sensitization of cervical cancer cells to radiation by the cyclin-dependent kinase inhibitor dinaciclib

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Abstract

Dinaciclib is a selective cyclin-dependent kinase inhibitor, but its radiosensitizing effect remains unclear. The aim of this study is to investigate the radiosensitizing effect of Dinaciclib on cervical cancer cells. Two cervical cancer cell lines, Hela and Siha, were selected, and the IC50 was determined by CCK8. The radiosensitizing effect of Dinaciclib was verified by plate cloning assay, and the G2/M phase arrest and apoptosis of IR cells were verified by flow cytometry. Immunofluorescence assay was used to verify the formation of γH2AX foci following DNA damage. Western blot was performed to detect cell cycle, apoptosis, autophagy, and DNA damage-related pathways. Dinaciclib increased the cell sensitivity to IR. IR induced G2/M phase arrest and apoptosis, and Dinaciclib enhanced this effect. Further, Dinaciclib delayed DNA repair, including non-homologous end joining repair and homologous recombination repair, and reduced the expression of DNA repair proteins Ku80 (SiHa cells), Ku70, and RAD51, as well as the expression of apoptotic marker Bcl-2. The expression of autophagy marker Beclin1 induced tumor cell death and increased the formation of DNA damage marker γH2AX foci. Dinaciclib improves the sensitivity of cervical cancer cells to IR by inducing cell cycle arrest, delaying DNA repair, and increasing apoptosis. However, further research is needed to unravel the complexity of DNA repair pathways.

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Data availability

The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.

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Funding

This work was supported by the Science and Technology Innovation Fund (Applied Basic Research) Project of Dalian City, Liaoning Province, China (Grant No. 2021JJ12SN40) and Validation project of artificial intelligence-assisted radioactive particle brachytherapy system for pelvic and abdominal tumors, Dalian City, Liaoning Province, China (Grant No. 2021JH1/10400051).

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Author notes

  1. Haichen Zhang and Tong Chu contributed equally to this work.

Authors and Affiliations

  1. Second Hospital of Dalian Medical University, 467 Zhongshan Road, Shahekou District, Dalian City, Liaoning Province, China

    Haichen Zhang, Tong Chu, Jin Zheng, Yun Teng, Ruilan Ma, Lijuan Zou & Haidong Zhao

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  1. Haichen Zhang
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  2. Tong Chu
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  3. Jin Zheng
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  4. Yun Teng
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  5. Ruilan Ma
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  6. Lijuan Zou
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  7. Haidong Zhao
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Contributions

All authors contributed to the study conception and design. Experimental design, data collation and analysis were performed by HZ, TC, YT and RM. Radiation therapy was performed by JZ during the experiment. The first draft of the manuscript was written by HZ and TC. LZ and HZ helped perform the analysis with constructive discussions. All authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

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Correspondence to Lijuan Zou.

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Zhang, H., Chu, T., Zheng, J. et al. Sensitization of cervical cancer cells to radiation by the cyclin-dependent kinase inhibitor dinaciclib. Med Oncol 40, 68 (2023). https://doi.org/10.1007/s12032-022-01890-x

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