18F-FDG Micro PET/CT imaging to evaluate the effect of BRCA1 knockdown on MDA-MB231 breast cancer cell radiosensitivity

Abstract

Objective: Radioresistance of tumor cells is a major factor associated with failure of radiotherapy (RT). This study aimed to investigate the effect of BRCA1 knockdown on MDA-MB231 breast cancer cell radiosensitivity. Materials and methods: Short hairpin RNA (shRNA) was used to knockdown BRCA1 gene in MDA-MB231 cells. Cell viability and proliferative capacity were assessed by CCK-8 and colony formation assays, respectively. We established xenograft models in nude mice to evaluate tumor volume and tumor weight. The mice were imaged by 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) before and after RT to evaluate changes in maximum standardized uptake value (SUVmax) and tumor SUVmax/muscle SUVmax (TMR). Changes in HIF-1α, Glut-1 and Ki-67 were analyzed and the correlation between 18F-FDG uptake and tumor biology was analyzed. Results: Compared with the control cells, RT significantly reduced cell viability and colony formation capacity in cells with the BRCA1 gene knockdown. In vivo assays showed that there was obvious delay in the tumor growth in the shBRCA1+RT group compared with the control group. 18F-FDG Micro PET/CT indicated a reduction in glucose metabolism in the shBRCA1+RT group, with statistically significant differences in both the SUVmax and TMR. The data showed the expression of HIF-1α, Glut-1 and Ki-67 was downregulated in the shBRCA1+RT group, and both SUVmax and TMR had significant correlation with tumor biology. Conclusion: These results demonstrated that BRCA1 knockdown improves the sensitivity of MDA-MB231 breast cancer cells to RT. In addition, 18F-FDG PET/CT imaging allows non-invasive analysis of tumor biology and assessment of radiosensitivity.

Keywords

• BRCA1
• Breast cancer
• Radiosensitivity
• Fluorodeoxyglucose
• PET/CT