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

Abstract

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.

Amphiphilic photosensitizer polymer as a nanocarrier of cytotoxic molecule for carrier‐free combination therapy

“…Then, IR-775 solution (1 mg/ml) was diluted by DMSO into different concentrations (0.333, 0.5, 1.0, 1.5, 2.0, 2.5, and 3.0 μg/ml). The PhA-PEG 5000 solution (10 mg/ml) was diluted into different concentrations (10,20,30,40,50,60,70, and 80 μg/ml). All the solutions of known concentrations were determined to obtain their corresponding absorbance.…”

“…Therefore, the combination of chemotherapy and PDT has been explored to achieve enhanced synergistic therapeutic effect and offer a new strategy for tumor with drug resisitance 4,5 . To achieve photo‐chemo combination therapy, many nanodrug delivery systems have been designed with various advantages, including co‐loaded drugs, improved tumor accumulation and less side effect to the healthy tissue 6–10 . However, most nanodrug delivery systems with complicated structures suffer from the problem of complicated fabrication process, and are difficult to achieve the clinical translation.…”

“…4,5 To achieve photo-chemo combination therapy, many nanodrug delivery systems have been designed with various advantages, including co-loaded drugs, improved tumor accumulation and less side effect to the healthy tissue. [6][7][8][9][10] However, most nanodrug delivery systems with complicated structures suffer from the problem of complicated fabrication process, and are difficult to achieve the clinical translation.…”

Pharmacological Activities of Aminophenoxazinones

“…Actinomycin D currently continues being studied. As an example of recent positive result, the increase of effectiveness for ovarian cancer treatment found for its synergic use with photodynamic therapy can be mentioned [36].…”

Three-Dimensional (3D) Culture Models in Cancer Investigation, Drug Testing and Immune Response Evaluation

“…A combined therapeutic regimen was also investigated by Layla Mohammad Hadi et al [ 7 ] in 2D and 3D ovarian cancer cell cultures. Photodynamic therapy and dactinomycin were tested at sub-lethal doses, showing a slightly higher efficacy in 2D systems compared to 3D systems.…”