Dose-effect relationship of photodynamic therapy on human non-small cell lung cancer in vivo
W. Suna (Dr), XY. Maa (Dr), GF. Wang*a (Dr)
a Peking University First Hospital, Beijing, CHINA
Background: Although photodynamic therapy (PDT) has gained increasing attention in treating lung cancer worldwide, current light dosimetry remains unclear that may affect the clinical efficacy. This study aimed to determine the optimal light dose on PDT by comprehensively evaluating macroscopic factors and microscopic apoptosis.
Methods: A model of subcutaneously implanted tumors using a lung adenocarcinoma cell line A549 in Balb/c nude mice has been established. The mice were injected with hematoporphyrin derivatives (3mg/kg) and irradiated superficially using 630 nm laser light 48 hours later at doses of 100, 200, 300, 400, and 500 J/cm2. The relative tumor volume (RTV), the tumor growth inhibition rate (TGI%) and complete remission (CR) rates were calculated. The assessment of apoptosis was performed after 4 weeks treatment.
Results: Compared to the untreated group, there was no difference in the RTV of 100 J/cm2 group, while the RTV of the other treatment groups (200, 300, 400, and 500 J/cm2) was significantly lower. In the 100 J/cm2 group, there were significant differences whether in the CR rates (0%) or the percentage of TGI% ≥75% (20%) compared with the other treatment groups (CR 56%~70%; TGI% 70%~90%), especially the 300 and 400 J/cm2 groups (CR 70%; TGI% 90%). In 300 and 400 J/cm2 groups, the expression of Caspase-3, PARP1, and Bax was increased significantly, and the Bcl-2 expression was significantly lower. Investigation of apoptotic mechanisms indicated that light dose could cause pathway activation differently by varying degrees of regulation of related molecules.
Conclusions: These results pinpoint the optimal dose on PDT of 300 and 400 J/cm2 showing considerable therapeutic potential for lung cancer, highlighting the light dose as a crucial factor in antitumor efficacy, which may have critical guiding implications for the clinical application.
Disclosure of funding source(s): none