Abstract 3839
Background
Multipotent cancer stem cells (CSC) are involved in micro-evolutionary tumor adaptation to therapeutic regimens. Due to their drug-resistance, they represent a promising target for treatment strategies of advanced prostate tumors. Fenofibrate (FF) has recently been pinpointed as a potential metronomic agent that augments the sensitivity of cancer cells to chemotherapeutic drugs. Here, we hypothesized that FF interferes with the drug-resistance of prostate cancer cell populations through the interference with the functions of cancer stem cell-like (SCL) cells.
Methods
Naïve and drug-resistant DU145 cells cultivated in control conditions and in the presence of DCX and/or FF were immunostained against pluripotency markers and analyzed with fluorescent microscopy, fluorescent activated cell sorting (FACS) and image stream.
Results
FACS analyses of naïve and docetaxel (DCX)-resistant DU145 cells revealed minute sub-populations of CD133+/CD44-, CD133+/CD44+ and CD133-/CD44+ SCL cells. SCL fractions were elevated within DCX-treated naïve and DCX-resistant DU145 cell line populations. More prominent increase of SCL-fraction was also observed in naïve, and to lower extent, in drug-resistant DU145 lineages upon combined DCX/FF treatment, which confirms their drug-resistance. CD44+ cells formed the aggregates of round and loosely attached cells, surrounded by morphologically diverse cellular clusters. These SCL cells offspring displayed neoplastic and invasive phenotype similar to that of parental cells; however, they showed increased, P-gp-dependent DCX- but not DCX/FF resistance. Loss of drug-resistance over time of SCL cells offspring was accompanied by induction of their EMT and invasive potential, and combined DCX/FF treatment interfered with this process.
Conclusions
These observations confirm the phenotypic plasticity of SCL cells and its role in the maintenance of prostate cancer cell heterogeneity and drug-resistance. FF can enhance the efficiency of palliative prostate cancer therapies through the interference with the function of cancer stem cells.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
Jagiellonian University, Faculty of Biochemistry, Biophysics and Biotechnology.
Funding
National Science Centre Poland.
Disclosure
All authors have declared no conflicts of interest.
Resources from the same session
5520 - Patient’s Usability Test results of a CINV Diary Application For Smartphones
Presenter: Paz Fernandez
Session: Poster Display session 3
Resources:
Abstract
2323 - Colorectal Telephone Assessment Pathway (CTAP) - A viable means of shortening time to a definitive diagnosis of Colorectal Cancer (CRC)
Presenter: Harriet Watson
Session: Poster Display session 3
Resources:
Abstract
6119 - Cancer Nursing and Social Media: Capturing the Zeitgeist
Presenter: Mark Foulkes
Session: Poster Display session 3
Resources:
Abstract
1776 - Examination of mobile applications on breast cancer
Presenter: AYDANUR AYDIN
Session: Poster Display session 3
Resources:
Abstract
4128 - E-health effectiveness to increase patient adherence for immunotherapy; a cost-benefit study.
Presenter: Maria José Dias
Session: Poster Display session 3
Resources:
Abstract
3219 - Experiences of internet-based stepped care among individuals with recently diagnosed cancer and symptoms of anxiety and/or depression
Presenter: Anna Hauffman
Session: Poster Display session 3
Resources:
Abstract
5010 - What do cancer patients know about their immunotherapy treatment?
Presenter: Mónica Arellano
Session: Poster Display session 3
Resources:
Abstract
4503 - Prospective Comparison of Travel Burden, Cost and Time to Obtain Tumor Board Treatment Plan Through In-Person Visits vs. an AI Enabled Health Technology (N=1803)
Presenter: Rajendra Badwe
Session: Poster Display session 3
Resources:
Abstract
4123 - Cancer care through the fire and flames: 3-year experience in the utilisation of electronic consultation and referral system at the Red Zone in Southern Thailand
Presenter: Nanthiya Rattanakhot
Session: Poster Display session 3
Resources:
Abstract
2087 - The effect of e-mobile education on the quality of life in women with breast cancer
Presenter: Derya ÇInar
Session: Poster Display session 3
Resources:
Abstract