Light dose effect of photodynamic therapy on growth inhibition and apoptosis induction in non-small cell lung cancer: A study in nude mouse model.

Abstract

Background: Photodynamic therapy (PDT) is receiving increasing attention in treating non-small cell lung cancer (NSCLC) worldwide, but in clinical practice, the relationship between treatment effect and PDT light dose in NSCLC remains unclear. Therefore, we aimed to determine the optimal light dose for PDT by exploring molecular biomarkers and evaluating tumor growth data.

Methods: We applied bioinformatics to identify promising genes and pathways in NSCLC and PDT. Then, the human lung adenocarcinoma cell line A549-bearing BALB/c nude mice were treated with hematoporphyrin derivative (HPD, 3 mg/kg) that is currently used widely for lung cancer treatment in the world even with photosensitization issues. After 48 h, tumor-bearing mice were irradiated superficially at doses of 100, 200, 300, 400, and 500 J/cm². The tumor growth data and apoptotic molecules were assessed and calculated.

Results: Bioinformatics results indicated that the apoptosis pathway was significantly enriched and caspase 3 was the most promising biomarker on prognosis in NSCLC-PDT. Compared to the untreated group, there was no difference in the relative tumor volume (RTV) of the 100 J/cm² group, while the RTV of the other treatment groups (200-500 J/cm²) was significantly lower. In the 100 J/cm² group, there were significant differences in the complete remission (CR, 0 %) and the percentage of tumor growth inhibition rate (TGI%) over 75 % (20 %) compared with the other treatment groups, especially the 300 and 400 J/cm² groups (CR 70 %; TGI% 90 %). In the 300 and 400 J/cm² groups, the expression of caspase 3, cleaved-caspase 3, PARP1, and Bax was increased significantly, while Bcl-2 expression was significantly lower.

Conclusions: Moderate doses of PDT (300 or 400 J/cm²) are more effective than low (100 or 200 J/cm²) or high doses (500 J/cm²) in the A549 tumor-bearing mice model. Since the A549 tumor is more akin to human tumors in pathological behavior, these experimental data may contribute to improving HPD-PDT illumination protocols for favorable clinical outcomes.