Synergy between Photodynamic Therapy and Dactinomycin Chemotherapy in 2D and 3D Ovarian Cancer Cell Cultures

• Published in: International journal of molecular sciences Vol. 21; no. 9; p. 3203
• Main Authors: Hadi, Layla Mohammad, Yaghini, Elnaz, MacRobert, Alexander J, Loizidou, Marilena
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI 30.04.2020; MDPI AG
• Subjects: actinomycin D; Antineoplastic Agents - pharmacology; Apoptosis - drug effects; Apoptosis - radiation effects; Cell Line, Tumor; Cell Survival - drug effects; Cell Survival - radiation effects; combination treatment; dactinomycin; Dactinomycin - pharmacology; Female; Humans; ovarian cancer; Ovarian Neoplasms - metabolism; photochemical internalisation; Photochemotherapy - methods; photodynamic therapy; dactinomycin; actinomycin D; 3D compressed collagen construct; photochemical internalisation; combination treatment; ovarian cancer; photodynamic therapy
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms21093203

In this study we explored the efficacy of combining low dose photodynamic therapy using a porphyrin photosensitiser and dactinomycin, a commonly used chemotherapeutic agent. The studies were carried out on compressed collagen 3D constructs of two human ovarian cancer cell lines (SKOV3 and HEY) versus their monolayer counterparts. An amphiphilc photosensitiser was employed, disulfonated tetraphenylporphine, which is not a substrate for ABC efflux transporters that can mediate drug resistance. The combination treatment was shown to be effective in both monolayer and 3D constructs of both cell lines, causing a significant and synergistic reduction in cell viability. Compared to dactinomycin alone or PDT alone, higher cell kill was found using 2D monolayer culture vs. 3D culture for the same doses. In 3D culture, the combination therapy resulted in 10 and 22 times higher cell kill in SKOV3 and HEY cells at the highest light dose compared to dactinomycin monotherapy, and 2.2 and 5.5 times higher cell kill than PDT alone. The combination of low dose PDT and dactinomycin appears to be a promising way to repurpose dactinomycin and widen its therapeutic applications.