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conferenceseries
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Volume 9, Issue 11 (Suppl)
J Cancer Sci Ther
ISSN: 1948-5956 JCST, an open access journal
Asia Pacific Oncologists 2017
November 20-22, 2017
November 20-22, 2017 Melbourne, Australia
14
th
Asia Pacific
Oncologists Annual Meeting
Effects of medroxyprogesterone acetate (MPA) in activating progesterone receptor signaling in benign
and cancer-associated fibroblasts of the endometrium
Ivy Chung, Omar I S, Adenan N A and Woo Y L
University of Malaya, Malaysia
M
edroxyprogesterone acetate (MPA) is used for conservative treatment for endometrial cancer (EC); however, patients
often develop progesterone resistance. Most typical and atypical endometrial hyperplasia shows regression after MPA
treatment. Primary type 1 EC responds moderately to MPA therapy (50-70%). Yet, MPA treatment only offers 10-20% response
rates and survival of less than one year in advanced and recurrent EC. It was shown that secretion from normal fibroblast
cells inhibit while cancer fibroblasts cells promote the proliferation of EC cells. Interestingly, a recent study showed that
progesterone receptor (PR) expression in normal fibroblast is important for progesterone inhibitory effects on cancer cells.
It has also been shown that estrogen is responsible for increasing PR expression. However, it is still largely unknown, if and
how, fibroblasts from endometrial cancers modulate EC response to progesterone. BAF and CAF were isolated from human
endometrial primary cultured cells using antibody-conjugated magnetic beads. Fibroblast and epithelial markers expression,
and progesterone receptor (PR) expression were determined using quantitative real-time PCR (qRT-PCR) and western
blotting. PR nuclear translocation was determines using immunofluorescence assay. Cell viability was determined using MTT
assay. Fibroblasts expressed high levels of fibroblast markers but not epithelial cell markers indicating minimal epithelial cells
contamination. Both BAF and CAF expressed varied levels of PR expression. PR nuclear translocation occurs within 6 hours
of 10 nM MPA treatment in BAFs and CAFs. Their response to MPA growth inhibition was similar (20% growth inhibition
when compared to vehicle) after treated with 1-400 nMMPA for 72 hours. The cell viability was 22% and 9% lower in BAFs and
CAFs, respectively following 100 nMMPA treatment in the presence of 10 nM E2 compared to MPA alone. Our data suggests
that PR signaling in CAF can be activated, and but has lower response to combination of MPA and estrogen treatment.
Biography
Ivy Chung is anAssociate Professor at Department of Pharmacology, Faculty of Medicine, University of Malaya, Malaysia. She is trained as a Cancer Pharmacologist
and interested in tumor microenvironment research. She has published numerous articles on tumor angiogenesis and cancer-associated fibroblasts. Her current
interest is to study hormonal and survival pathways that are activated in the tumor-host cell interaction that could contribute to aggressiveness of the cancer as well
as to development of therapy resistance.
ivychung@ummc.edu.myIvy Chung
et.al., J Cancer Sci Ther 2017, 9:11 (Suppl)
DOI: 10.4172/1948-5956-C1-117