The role of FOS-mediated autophagy activation in the indocyanine green-based photodynamic therapy for treating melanoma

Abstract

The morbidity and mortality of melanoma which accounts for 90% of cutaneous neoplasm-related deaths is growing over the last few decades. Common treatments for melanoma are limited to poor tissue selectivity, high toxicity and drug resistance. Photodynamic therapy (PDT) is an effective adjuvant therapy and could be a promising therapy for melanoma. Multiple mechanisms are involved in PDT² and programmed cell death (PCD) which comprises of autophagy and apoptosis is likely to be a critical one. Whereas, the molecular mechanism and subsequent effect of PDT-induced autophagy in melanoma are still unclear. In this study, we first analyzed gene expression data in the TCGA³ and GEO⁴ databases to clarify that PDT-induced-autophagy improved the prognosis of melanoma. The expression of FOS which generally defined as an immediate-early gene (IEG) and related to cell autophagy was found significantly elevated after PDT. To further investigate whether FOS played a key role in PDT-induced-autophagy of melanoma, we first determined the optimum concentration of ICG solution for autophagy observation. Then, relative FOS expression was detected at mRNA and protein level and cell autophagy was observed by western blot and flow cytometry. We found that ICG-PDT treatment could significantly elevate FOS expression in SKCM⁵ B16 cells, and FOS promoted ICG-PDT-induced cell autophagy. To sum up, our data indicated that FOS was involved in ICG-PDT-induced-autophagy in melanoma and furthermore improved the prognosis of melanoma.

Keywords: Autophagy; FOS; Melanoma; Photodynamic therapy.