Rosiglitazone enhances radiosensitivity by inhibiting repair of DNA damage in cervical cancer cells.

Abstract

Radiation therapy (RT) is one of the main treatment modalities for cervical cancer. Rosiglitazone (ROSI) has been reported to have antiproliferative effects against various types of cancer cells and also to induce antioxidant enzymes that can scavenge reactive oxygen species (ROS) and thereby modify radiosensitivity. Here, we explored the effect of ROSI on radiosensitivity and the underlying mechanisms in cervical cancer cells. Three cervical cancer cell lines (ME-180, HeLa, and SiHa) were used. The cells were pretreated with ROSI and then irradiated. Expression of proteins of interest was detected by western blot and immunofluorescence. Intracellular production of ROS was measured by H2DCFDA. Radiosensitivity was assessed by monitoring clonogenic survival. Expression of antioxidant enzymes (catalase, superoxide dismutases) was increased by ROSI in HeLa and SiHa cells, but not in ME-180 cells. With ROSI pre-treatment, cell survival after irradiation remained unchanged in HeLa and SiHa cells, but decreased in ME-180 cells. Radiation-induced expression of γ-H2AX was increased and that of RAD51 was decreased by ROSI pre-treatment in ME-180 cells, but not in HeLa cells. ROSI increases radiosensitivity by inhibiting RAD51-mediated repair of DNA damage in some cervical cancer cell lines; therefore, ROSI is a potential inhibitor of RAD51 that can be used to enhance the effect of RT in the treatment of some cervical cancers.

• Authors: Zhengzhe An, Jae-Ran Yu, Woo-Yoon Park
• Journal: Radiation and environmental biophysics (Radiat Environ Biophys) Vol. 56 Issue 1 Pg. 89-98 (03 2017) ISSN: 1432-2099 [Electronic] Germany
• PMID: 28184999 (Publication Type: Journal Article)

Chemical References

• Radiation-Sensitizing Agents
• Reactive Oxygen Species
• Thiazolidinediones
• Rosiglitazone
• Catalase
• Superoxide Dismutase

Topics

• Catalase (metabolism)
• Cell Line, Tumor
• Cell Survival (drug effects, radiation effects)
• DNA Damage
• DNA Repair (drug effects, radiation effects)
• Female
• Gene Expression Regulation, Neoplastic (drug effects, radiation effects)
• Humans
• Intracellular Space (drug effects, metabolism, radiation effects)
• Radiation Tolerance (drug effects)
• Radiation-Sensitizing Agents (pharmacology)
• Reactive Oxygen Species (metabolism)
• Rosiglitazone
• Superoxide Dismutase (metabolism)
• Thiazolidinediones (pharmacology)
• Uterine Cervical Neoplasms (pathology)