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
4096 - Patient experience and use of an intervention combining nurse-led telephone and technologies for the monitoring of oral cancer medication
Presenter: Marie Ferrua
Session: Poster Display session 3
Resources:
Abstract
6042 - Harnessing nurse leadership to implement a project for electronic scheduling of chemotherapy
Presenter: Emma Masters
Session: Poster Display session 3
Resources:
Abstract
3123 - Turkish Cancer Patients’ Preference for Information and Communication Technologies
Presenter: Esra ildes
Session: Poster Display session 3
Resources:
Abstract
6062 - Unmet Needs in Oncology Research related to radiological response evaluation: a multi-center survey in three European countries
Presenter: Sophie Nisse Durgeat
Session: Poster Display session 3
Resources:
Abstract
6109 - A program implementation to facilitate intraoperative brachytherapy between hospitals
Presenter: Marc Garcia Casellas
Session: Poster Display session 3
Resources:
Abstract
1772 - Using Mobile-Based Health Care Applications Outcomes: Mini Systematic Review
Presenter: Aydanur Aydin
Session: Poster Display session 3
Resources:
Abstract
2792 - Evaluation of an education program for cancer patients receiving chemotherapy
Presenter: Iraqi Amina
Session: Poster Display session 3
Resources:
Abstract
3715 - iGestSaúde: Application for self-management of symptoms during chemotherapy treatment
Presenter: Bruno Magalhaes
Session: Poster Display session 3
Resources:
Abstract
3854 - Palliative care requirements of cancer patients and investigation of knowledge and expectations related to palliative care of the patients and their families
Presenter: Ozlem Topkaya
Session: Poster Display session 3
Resources:
Abstract
4997 - Hospice care, what to expect? An exploration of the expectation of future hospice patients
Presenter: Merel van Klinken
Session: Poster Display session 3
Resources:
Abstract