Abstract Objective: The aim of this study was to detect the apoptosis of A549 lung cancer cells after paeonol combined with 125I seed brachytherapy by 99Tcm-Annexin V imaging and analysis of apparent diffusion coefficient(ADC) values of the magnetic resonance diffusion-weighted imaging(DWI). Methods: Fifty-two nude mice bearing human lung cancer cell line A549 were randomly divided into 4 groups(13 mice in each group). Group A: paeonol treatment alone. Group B: 125I seed brachtherapy alone. Group C: combination of paeonol and 125I seed brachtherapy. Group D: cold seed implantation as the control group. 10~14 days after brachytherapy, all mice were performed DWI and 99Tcm-Annexin V imaging, and then all mice were sacrificed, the tumor weights and dimensions of survived mice were measured, tumor weight inhibition rate was calculated, tumor cell apoptosis was detected by terminal oxynucleotidy transferase mediated dUTP biotin nick end labeling(TUNEL) immunofluorescence. Results: After the intervention of paeonol, 125I seed brachtherapy and their combination therapy, the growth of tumor cells were significantly inhibited, tumor volume and quality decreased obviously compared with the control group, the tumor inhibitory rates were 35.6%, 57.3% and 74.4%, respectively. The difference in positive rate of 99Tcm-Annexin V imaging between group A, B, C and D were statistically significant(χ2=9.35, P=0.025); Compared with group D, paeonol(χ2=4.51, P=0.031), 125I seed brachtherapy(χ2=7.96, P=0.004) and the combination of both(χ2=15.48, P<0.001) all could increased the positive rate of 99Tcm-Annexin V imaging. There were significant differences in the tumor uptake of 99Tcm-Annexin V(T/N) and the ADC values between groups(F=7.218, 6.987, both P<0.05), and the T/N and ADC values in group A, B and C were higher than that in group D, and the rise in group C was especially obvious(all P<0.05). The combination of paeonol and 125I seed brachtherapy enhanced cell apoptosis, and the apoptosis index(AI) between groups had statistically significant difference(F=5.123, P=0.038). The ADC value was correlated with AI and T/N(r=0.748, 0.782, P=0.032, 0.016), and AI was correlated with T/N(r=0.765, P=0.024). Conclusion: Paeonol can enhance the anti-tumor effect combined with 125I seed brachytherapy, the mechanism may be related to induced cell apoptosis. 99Tcm-Annexin V imaging combined with the analysis of ADC value could early effectively detect the apoptosis of tumor cells, thus they as visual have the potential to predict efficacy in vivo.
DENG Yong-mei,LI Yuan,ZHANG Jin-shan, et al. Observation of apoptosis of A549 lung cancer in nude mice induced by paeonol combined with#br#
125I seed brachytherapy[J]. JOURNAL OF CHINA MEDICAL IMAGING, 2017, 28(9): 628-632.
2017, Vol. 28 
