Potential therapeutic efficacy of photodynamic therapy on female hormonal-dependent cancers in a hormonal simulated microenvironment.

BACKGROUND: Photodynamic Therapy (PDT) is a clinically approved cancer treatment. Sex hormones, the key drivers for the development of female hormonal dependent cancers, might affect cancer treatment. There are seldom studies to evaluate the effect of sex hormones mimicked the menstrual cycle on the PDT mediated by prodrug 5-aminolevulinic acid (ALA) and its ester derivatives to the hormonal dependent cancers. AIMS: To evaluate the efficacy of sex hormones on Hexyl-ALA-PDT in hormonal dependent cancers and the effect of the sex hormones on heme biosynthetic pathway. METHODS: Cell culture system that mimicked the fluctuation of sex hormones 17ß-estradiol (E2) and progesterone (PG) in the menstrual cycle was developed. Two pairs of hormonal-independent and hormonal dependent uterine sarcoma and breast cancer cell lines were used as cell models. Hexyl-ALA induced PpIX production and intracellular localization were examined. Key enzymes for PpIX synthesis were analysed. Hexyl-ALA-PDT mediated phototoxicity was evaluated. RESULTS: The PpIX generation was increased in the hormonal-dependent cells (28-50 %) when cultured in the hormonal microenvironment with long incubation of Hexyl-ALA for 15 and 24 h compared to that cultured without hormones; whereas only slight difference in PpIX generation in their hormonal-independent counterpart. The PpIX generation was in a time-dependent manner. The CPOX, PPOX and FECH expressions were significantly enhanced by Hexyl-ALA-PDT in uterine sarcoma cells in hormonal microenvironment. Hexyl-ALA-PDT triggered significant increase of PPOX expression in breast cancer cells in hormonal microenvironment. The Hexyl-ALA-PDT phototoxicity was enhanced by 18-40 % in cells cultured in the hormonal system in a dose-dependent manner. CONCLUSION: The PpIX generation and the efficacy of Hexyl-ALA-PDT in both uterine sarcoma and breast cancer cells was significantly enhanced by the sex hormones via cultured in the hormonal microenvironment.

Comparative study of FosPeg® photodynamic effect on nasopharyngeal carcinoma cells in 2D and 3D models.

Photodynamic Therapy (PDT) offers an alternative option for the treatment of nasopharyngeal carcinoma (NPC). The utilization of 3-dimensional (3D) culture model might provide better understanding of PDT effects on NPC cells. The aim of this in vitro study was to compare PDT effect on NPC cells using 2D and 3D models. Two 3D culture models were established using liquid overlay method with agarose base (MCL) and hanging drop method (MCS). PDT was carried out using the combination of FosPeg® and 652 nm laser in 3D and conventional 2D models. The effects of 3D culture size and morphology on the uptake and distribution of sensitizer and gene expression were examined. Photocytotoxity, mode of cell death, and protein expression were compared for 2D and 3D models. Regular and irregular NPC spheroids were obtained from MCL and MCS methods, respectively. A significantly down-regulation of LMP1 mRNA were observed in MCL spheroid. The sensitizer uptake in 3D spheroids was half of 2D culture. More sensitizers were required to obtain IC50 in 3D spheroids. Apoptosis, necrosis and autophagosomes were detected in PDT treated 2D and 3D cells. Different protein expression patterns were observed in 2D and 3D models. FosPeg® PDT is effective in killing NPC cells. MCL-derived 3D spheroid model is more suitable for the evaluation of PDT killing mechanisms.