Photodynamic therapy enhances dacarbazine sensitivity of melanoma cells by induction of apoptosis and downregulation of PI3K/AKT signaling pathway

Dacarbazine (DTIC) is a crucial drug for treating melanoma, but resistance to it poses a significant challenge to effective chemotherapy. Photodynamic therapy (PDT), a minimally invasive, repeatable, and highly selective anti-cancer treatment, has shown promise in recent studies as a potent modulator of chemotherapy sensitivity in different cancerous cells. This investigation aims to explore the effect of photodynamic treatment on the DTIC sensitivity of melanoma cells. The SKMEL-3 melanoma cells were treated with PDT and DTIC, separately or in combination. The toxicity consequences of these treatments were studied using MTT test. This assay was used to analyze the cytotoxic effects of these treatments, and increased DTIC sensitivity was observed in SK-MEL-3 cells following pre-treatment with PDT. Additionally, flow cytometry analysis showed sub-G1 phase cell cycle arrest and increased apoptosis in all treatment groups. Alterations in the expression levels of caspases (3, 8, 9) and Bcl-2 genes further confirmed that apoptosis was more pronounced in the combination group. Moreover, combining PDT with DTIC significantly downregulated the expression of PI3K, AKT, and mTOR, while upregulating PTEN. Our data suggest that all mentioned treatments significantly reduce cell migration by downregulating MMP-2 and MMP-9 and decrease clonogenicity by downregulating SOX2 and OCT4 in SK-MEL-3 cells, with these effects being more evident after combination treatment. In conclusion, our findings highlight the potential of PDT pre-treatment to enhance DTIC sensitivity in SK-MEL-3 cells and suggest that the combination therapy is a promising strategy for further research in melanoma treatment.