Acta Pharmacologica Sinica (2009) 30: 458-466; doi: 10.1038/aps.2009.18

Acta Pharmacologica Sinica (2009) 30: 458-466; doi: 10.1038/aps.2009.18; published online 9th March 2009

Original Article

Adenovirus-mediated expression of UHRF1 reduces the radio-sensitivity of cervical cancer HeLa cells to γ-irradiation

Xin-li LI¹, Qing-hui MENG², Sai-jun FAN^{1, 2,}*

¹School of Radiology and Public Health, Soochow University, Suzhou 215123, China; ²Department of Oncology, Lombardi Comprehensive Cancer Center, Georgetown University, Washington, DC 20057, USA

Aim: An in vitro study was carried out to determine the effect of UHRF1 overexpression on radiosensitivity in human cervical cancer HeLa cells using adenovirus-mediated UHRF1 gene transfer (Ad5-UHRF1).

Methods: Cell survival was evaluated using the clonogenic survival assay and the MTT assay; apoptosis and cell cycle distribution were monitored by flow cytometry. Protein levels were measured by Western blotting. Silencing XRCC4 expression was performed by transfection of small interfering RNA (siRNA).

Results: Increased expression of UHRF1 by Ad5-UHRF1 significantly reduced the radiosensitivity of HeLa cells. The UHRF1-mediated radioresistance was correlated with increased DNA repair capability and increased expression of the DNA damage repair protein, XRCC4. Knocking down XRCC4 expression in the cells using XRCC4 siRNA markedly reduced the UHRF1-mediated radioresistance.

Conclusion: These results provide the first evidence for revealing a functional role of UHRF 1 in human cervical cancer cells as a negative regulator of radiosensitivity.

Keywords: UHRF1; HeLa cells; radiosensitivity; XRCC4; DNA repair

This work was supported by the Jiangsu Province “Liu Da Ren Cai Gao Feng" Project (No 06-C-004), the National Natural Science Foundation of China (No 30672435) and the Innovation Fund for Small Technology-Based Firms of China (No 06C 26223201098).

* Correspondence to Sai-jun FAN.
E-mail sjfan@suda.edu.cn or sf88@georgetown.edu
Received 2009-01-04 Accepted 2009-02-05

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