Abstract

Abstract Cutaneous melanoma represents the most lethal form of skin cancer and remains refractory to current therapies. Failure of treatment has been attributed to the over-expression of ABC transporters. Alternative combinatorial approaches comprising chemotherapeutics and photodynamic therapy have been proposed to overcome resistance. The aim of this study was therefore to use the chemotherapeutic drug dacarbazine (DTIC), together with PDT on pigmented and unpigmented metastatic melanoma cell lines in vitro to assess efficacy and potentially identify mechanisms of resistance. We show a possible synergism of PDT+DTIC in reducing melanoma cell viability in vitro. At 24h post-treatment, only the unpigmented melanomas were sensitive to DTIC treatment (20-25% death at 1250µM). At 48h, a lethal dose of 50% was reached in these cells in contrast to the pigmented melanoma (20% at 48h). The same trend was observed with the combination therapy (PDT+DTIC) at both timepoints. Furthermore, PDT+DTIC suppressed the self-renewal capacity of both melanoma cell lines. No significant differences in ABCG2 protein expression was found at 24h post-treatment. Overall, these results suggest that ABCG2 transporters may not play a role in melanoma resistance to therapies and thus further work is required to elucidate the clinical efficacy of combination treatments in the fight against skin cancer. Citation Format: Fleury Augustin Nsole-Biteghe, Olawale Ajuwon, Lester M. Davids. An investigation into the synergistic action of chemotherapy and photodynamic therapy (PDT) in resistant human melanoma [abstract]. In: Proceedings of the AACR International Conference: New Frontiers in Cancer Research; 2017 Jan 18-22; Cape Town, South Africa. Philadelphia (PA): AACR; Cancer Res 2017;77(22 Suppl):Abstract nr B42.

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