Abstract
Background and Purpose The aim of this study was to evaluate the radiosensitizing effect of oleanolic acid (OA) on C6 rat glioma and the changes in tumor biology during radiosensitization therapy on 18F-fluoromisonidazole (18F-FMISO) positron emission tomography/computed tomography (PET/CT). Methods The radiosensitizing effect of OA on C6 tumors was assessed in vivo by measuring the tumor inhibitory rate and rat survival time. Meanwhile, rats with C6 tumors were imaged with 18F-FMISO PET/CT during radiosensitization therapy. Tumor-to-muscle ratio (TMR) of 18F-FMISO maximum uptake was calculated by region of interest analysis. Changes in tumor biology after therapy were assessed with immunohistochemical staining. 18F-FMISO uptake was analyzed in relation to expression of tumor biomarkers including hypoxia-inducible factor (HIF)-1α, glucose transporter (Glut-1), the proliferation antigen Ki67, tumor suppressor P53, and microvessel density (MVD). Results The results showed that OA combined with radiation inhibited the growth rates of tumors and prolonged the survival period of tumor-bearing rats effectively (χ2 = 12.5, p < 0.01). 18F-FMISO PET/CT indicated decreases in hypoxia after radiosensitization therapy. Statistical differences were observed in TMR of the irradiation group and OA combined with irradiation group (t = 3.32, p < 0.05). HIF-1α, Glut-1, Ki67, P53, and MVD expressions in tumors were downregulated by OA combined with radiation as well as with radiation alone. Additionally, there was a significant positive linear correlation between TMR and HIF-1α, Glut-1, Ki67, P53, and MVD. Conclusions These results suggest that OA has a radiosensitizing effect on C6 tumors in terms of tumor volume inhibition, survival extension, and multiple poor prognosis biological markers downregulation. 18F-FMISO PET/CT can be of value for tumor biology noninvasive capture and radiosensitization response evaluation.
Highlights
The 2015 Nobel Prize in Physiology or Medicine was awarded to Chinese scientist Professor Youyou Tu for her outstanding contribution to the discovery of the antimalarial effects of the Chinese herb Artemisia annua L. [1]
The threshold for hypoxia based on to-muscle ratio (TMR) was set at 1.2; hypoxia was found in 91.7% (22/24) of C6 tumors imaged prior to therapy. 24 h after different therapies, the proportions of hypoxic tumors in the control group, oleanolic acid (OA) group, IR group, and OA combined with IR group were 100% (6/6), 100% (6/6), 66.7% (4/6), and 33.3% (2/6), respectively
TMR rates of the IR group and the OA combined with IR group were 3.12% and 11.54%, respectively
Summary
The 2015 Nobel Prize in Physiology or Medicine was awarded to Chinese scientist Professor Youyou Tu for her outstanding contribution to the discovery of the antimalarial effects of the Chinese herb Artemisia annua L. [1]. The aim of this study was to evaluate the radiosensitizing effect of oleanolic acid (OA) on C6 rat glioma and the changes in tumor biology during radiosensitization therapy on 18F-fluoromisonidazole (18F-FMISO) positron emission tomography/computed tomography (PET/CT). Rats with C6 tumors were imaged with 18F-FMISO PET/CT during radiosensitization therapy. 18F-FMISO uptake was analyzed in relation to expression of tumor biomarkers including hypoxia-inducible factor (HIF)-1α, glucose transporter (Glut1), the proliferation antigen Ki67, tumor suppressor P53, and microvessel density (MVD). The results showed that OA combined with radiation inhibited the growth rates of tumors and prolonged the survival period of tumor-bearing rats effectively (χ2 = 12.5, p < 0.01). These results suggest that OA has a radiosensitizing effect on C6 tumors in terms of tumor volume inhibition, survival extension, and multiple poor prognosis biological markers downregulation. These results suggest that OA has a radiosensitizing effect on C6 tumors in terms of tumor volume inhibition, survival extension, and multiple poor prognosis biological markers downregulation. 18F-FMISO PET/CT can be of value for tumor biology noninvasive capture and radiosensitization response evaluation
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
