Abstract
Introduction: Sex hormones are the key factors that limit the effectiveness of conventional cancer treatments especially in patients with sex-hormone-dependent cancers. Estrogen/17b-estradiol (E2) and progesterone (P) are two major sex hormones whose levels fluctuate during the menstrual cycle. Studies reported that hormonal therapy with E2/P is highly associated with increased risk and progression of gynaecological cancers, such as uterine sarcoma and ovarian cancer. Photodynamic Therapy (PDT) is an FDA approved cancer treatment. Our previous studies showed that hexyl-ALA mediated PDT is effective to uterine sarcoma in vitro. Uterine sarcoma is a hormonal dependent cancer, patients with uterine sarcoma might be affected by the presence of hormones. This study aims to investigate the effect of hexyl-ALA-PDT in uterine sarcoma in a simulated hormonal microenvironment.
Methods: Flow cytometry and MTT assay were applied to determine the intracellular PpIX generation and the phototoxicity mediated by hexyl-ALA-PDT respectively in the proposed cells with the presence of hormones.Results: The PpIX generation and accumulation induced by hexyl-ALA in the proposed cells were increased by 15% and 20% when supplemented with the hormones and with the hormones and ferrochelatase inhibitor respectively. In the hormonal microenvironment, the phototoxicity mediated by hexyl-ALA-PDT was enhanced 30% at 2J/cm2.
Conclusion: The simulated hormonal microenvironment significantly enhanced hexylALA-PDT efficacy in uterine sarcoma cells. These two sex hormones might modulate the heme biosynthetic pathway to increase the PpIX accumulation; thus more indepth mechanistic studies with hormonal enhancement on hexyl-ALA-PDT efficacy deserved to be delineated.
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).
Methods: Flow cytometry and MTT assay were applied to determine the intracellular PpIX generation and the phototoxicity mediated by hexyl-ALA-PDT respectively in the proposed cells with the presence of hormones.Results: The PpIX generation and accumulation induced by hexyl-ALA in the proposed cells were increased by 15% and 20% when supplemented with the hormones and with the hormones and ferrochelatase inhibitor respectively. In the hormonal microenvironment, the phototoxicity mediated by hexyl-ALA-PDT was enhanced 30% at 2J/cm2.
Conclusion: The simulated hormonal microenvironment significantly enhanced hexylALA-PDT efficacy in uterine sarcoma cells. These two sex hormones might modulate the heme biosynthetic pathway to increase the PpIX accumulation; thus more indepth mechanistic studies with hormonal enhancement on hexyl-ALA-PDT efficacy deserved to be delineated.
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).
Original language | English |
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Pages (from-to) | S339 |
Number of pages | 1 |
Journal | Annals of Oncology |
Volume | 32 |
Issue number | Supplement 4 |
Early online date | 26 Jul 2021 |
DOIs | |
Publication status | Published - Jul 2021 |
Externally published | Yes |
Event | Virtual Congress 2021 the Japanese Society of Medical Oncology Annual Meeting - Online Duration: 18 Feb 2021 → 21 Feb 2021 http://www.congre.co.jp/jsmo2021/en/greeting/index.html (Link to conference website) |