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e-Posters

46P - Enhanced 5-aminolevulinic acid (ALA)-based photodynamic therapy (PDT) Efficacy by hormones in uterine sarcoma cells via upregulation of proporphyrinogen oxidase

Date

06 Oct 2021

Session

e-Posters

Presenters

Ellie Chu

Citation

Annals of Oncology (2021) 32 (suppl_6): S1345-S1371. 10.1016/annonc/annonc740

Authors

E.S.M. Chu1, H. Lau2, Z. Huang3

Author affiliations

  • 1 TWC-Tung Wah College:King's Park Campus, Kowloon/HK
  • 2 TWC-Tung Wah College:King's Park Campus, 852 - Kowloon/HK
  • 3 Fujian Normal University, 86 - Fuzhou/CN
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Abstract 46P

Background

Photodynamic therapy (PDT) is an FDA approved cancer treatment modality for various cancers. In principle, PDT induces a photochemical reaction with exogenous photosensitizer (PS) in cancer cells upon light irradiation with oxygen, which generates reactive oxygen species leading to cancer cell death. Studies showed that hormones enhanced accumulation of photosensitive protoporphyrin IX (PpIX) generated by ALA PS in human endometrial cells, implying the increased PpIX potentially boost up ALA-based PDT effect in hormonal dependent cancers. Yet the underlying mechanism remains unexplored.

Methods

Uterine sarcoma cells were cultured with fluctuated 17β-estradiol (E2) and progesterone (P) levels as human menstrual cycle, then treated with exogenous Hexyl-ALA compared with normal cultured cells. PpIX localization and accumulation in the cells were determined by confocal microscopy and flow cytometry respectively. Hexyl-ALA-PDT effect was evaluated by MTT assay with sulfentrazone (Sul) inhibitor of proporphyrinogen oxidase (PPOX) - a limiting factor of PpIX in the heme pathway. The PPOX expression in cells was quantified by flow cytometry.

Results

PpIX localized in mitochondria. PpIX accumulation increased 30% with E2 and P in a time-dependent manner compared with hexyl-ALA (30 μM) only. At 4hr, the phototoxicity increased from 20% to 60% at hexyl-ALA (30 μM, 2J/cm2) compared with hormones respectively. Addition of Sul further enhanced the phototoxicity to 70%. PPOX level also enhanced by hormones; implying the hormonal microenvironment boost up Hexyl-ALA-PDT effect in the cells via up-regulation of PPOX.

Conclusions

This study showed that hormones played a vital role in enhancing hexyl-ALA PDT effect via up-regulation of PPOX. The simulated hormonal microenvironment culture model is suitable to study hexyl-ALA-PDT effect in hormonal dependent cancers.

Legal entity responsible for the study

The authors.

Funding

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

Disclosure

All authors have declared no conflicts of interest.

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