Photodynamic efficacy via modulation of signal pathways on chemoresistant small cell lung cancer (SCLC) cells

A25 Introduction: Lung cancer is the leading cause of cancer death worldwide. Small cell lung cancer (SCLC) is associated with the poorest prognosis. Photodynamic therapy (PDT) is a new approach of cancer treatment. It works by generating singlet oxygen to induce cancer cell death in the presence of photosensitizers, light and oxygen. Photosensitizer - NPe6 may be useful for treating SCLC patients.
 Aims: To evaluate the anti-tumour effect and mechanism of the photosensitizer NPe6 - PDT in chemo-resistant cell line H69AR SCLC.
 Method: The optimal uptake of NPe6 in H69AR cells was measured by flowcytometer. Phototoxicity of NPe6-PDT to the cells was evaluated by automated cell viability analysis. The expression of tumor suppressor protein p53, the anti-apoptotic protein BCl 2 , p38 mitogen-activated protein kinase (p38 MAPK) and c-jun N-terminal protein kinases (JNKs) were analyzed by Western blot. Morphological apoptotic changes in H69AR cells after treatment were determined by DAPI under microscopic examination.
 Results: The optimal cellular uptake of NPe6 was at 4 hours incubation. The phototoxicity of NPe6-PDT induced 75% killing in H69AR cells at 20μg/mL and 4 J/cm 2 . The expression of BCl 2 was down-regulated while the level of p53 remained after treatment. The expressions of phosphorylated p38 MAPK and JNK proteins were also down-regulated post-PDT treatment. Up to 50% of cells at LD 75 .showed condensed nucleus using DAPI nuclear stain, reflecting cells undergoing apoptosis.
 Conclusion: NPe6-PDT is effective to H69AR cells causing death through apoptosis. It may be mediated by suppressing the anti-apoptotic protein BCl 2 expression and down-regulating the phosphorylated p38MAPK and JNKs. Further cellular protein modulations after treatment will be elucidated.