248P - The effect of progesterone on ALA-based PDT efficacy in uterine sarcoma cells

Background

Photodynamic Therapy (PDT) is an FDA approved cancer treatment. Hexyl-ALA, one of the 5-aminolevulinic acid (ALA) derivatives, induces higher protoporphyrin IX (PpIX) accumulation in cancer cells through the disrupted heme pathway. Upon specific light activation with oxygen, reactive oxygen species will be released for cancer cell destruction. Studies also revealed that ALA induced higher PpIX accumulation with hormonal supplement. Uterine sarcoma is a hormonal dependent gynecological cancer. Addition of hormones with ALA-PDT might be a new therapeutic approach.

This study aimed to demonstrate the effect of progesterone on hexyl-ALA-PDT in uterine sarcoma cells; the in-depth mechanism related to heme pathway is yet to be explored.

Methods

The intracellular PpIX generation and the phototoxicity mediated by Hexyl-ALA-PDT with progesterone were determined by flow cytometry and MTT assay respectively in the proposed cells.

Results

The PpIX generation and accumulation induced by hexyl-ALA in the proposed cells were increased in 10% and 30% when supplemented with progesterone and with progesterone and ferrochelatase inhibitor respectively. The progesterone enhanced hexyl-ALA-PDT effect from lethal dose of 20 (LD₂₀) to lethal dose of 60 (LD₆₀) at 2J/cm².

Conclusions

Progesterone significantly enhanced hexyl-ALA-PDT efficacy in uterine sarcoma cells. Progesterone might enhance the efficacy of Hexyl-ALA-PDT through the modulation of heme biosynthetic pathway; thus in-depth mechanistic studies of hormonal enhancement on Hexyl-ALA-PDT efficacy deserved to be explicit.

Acknowledgement

Hexyl-ALA was kindly provided by Photocure ASA. This study was fully supported by a grant from the Research Grants Council (RGC) of the Hong Kong Special Administrative Region, China (Project no.: UGC/FDS17/M06/19).

Clinical trial identification

Editorial acknowledgement