Literature DB >> 29872938

The poly (ADP-ribose) polymerase inhibitor rucaparib suppresses proliferation and serves as an effective radiosensitizer in cervical cancer.

Mei Tang1, Qiuli Liu1, Leyuan Zhou2, Ling Chen1, Xueqing Yang1, Jinjin Yu2, Yuan Wang3, Haifeng Qiu4.   

Abstract

Objectives Our goal was to investigate the effects of rucaparib on the proliferation of cervical cancer cells and sensitivity to radiotherapy. Methods We used the human cervical cancer cell lines Hela and Siha and evaluated their viability and activity using various methods. Cellular proliferation was assessed by CCK-8 and clonogenic assays after treatment with rucaparib. Cell cycle analysis was performed using propidium iodide staining. Western immunoblotting analysis was used to detect the expression of cyclin D1 and CDK4. Immunofluorescence staining assay was performed to detect the expression of the DNA injury marker ץ-H2AX after treatment with rucaparib and radiotherapy. Animal experiments were also performed to evaluate tumor size after treatment with rucaparib. Immunohistochemistry was performed to analyze the expression of Ki-67. Results Rucaparib suppressed proliferation, induced G2/M phase arrest, and reduced the expression of cyclin D1 and CDK4 in cervical cancer cells. When rucaparib was combined with radiotherapy in cervical cancer cells, clone formation decreased significantly and G2/M phase arrest was accentuated. The expression of the DNA-damage marker ץ-H2AX was increased significantly, and rucaparib suppressed tumor growth in vivo. Conclusions Rucaparib exerts significant anti-proliferative effects and can serve as an effective radiosensitizer in cervical cancer, suggesting its candidacy in cervical cancer treatment and worthiness for further investigation.

Entities:  

Keywords:  Cervical cancer; Proliferation; Radiosensitivity; Rucaparib

Mesh:

Substances:

Year:  2018        PMID: 29872938     DOI: 10.1007/s10637-018-0616-7

Source DB:  PubMed          Journal:  Invest New Drugs        ISSN: 0167-6997            Impact factor:   3.850


  29 in total

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