Abstract 3842
Background
Metronomic approach represent a promising strategy for the chemotherapy of drug-resistant tumors, because it can reduce the effective doses and adverse effects of chemotherapeutics. In particular, metabolic blockers reduce energy supply for multi-drug resistance systems, thus increasing tumor cells’ reactivity to chemotherapeutics. Metformin is an anti-diabetic drug that blocks mitochondrial respiration, interferes with ATP production and with proliferation of cancer cells. However, the effect of drug-resistance of prostate cancer cells on their reactivity to metformin has not yet been evaluated.
Methods
Here, we analysed short- and long-term cytotoxic and pro-apoptotic effects of metformin on the phenotype of human prostate cancer PC-3 and DU145 cells and their docetaxel (DCX)-resistant lineages (PC-3-DCX20 and DU145_DCX20; obtained after long-term treatment with 20 nM DCX). We concentrated on their DCX-resistance pattern and compared their epithelial-mesenchymal transition (EMT)-related phenotype, invasive potential and the activity of ATP-binding cassette (ABC) transporters in the presence of metformin and/or DCX.
Results
Metformin increased the sensitivity of drug-resistant PC-3 and DU145 cells to DCX; even though PC-3_DCX20 cells displayed reduced sensitivity to combined metformin/DCX treatment. When administered alone, metformin exerted less prominent cytostatic effects on PC_DCX20 cells than on their DU145_DCX20 counterparts. This effect was accompanied by EMT-related morphological changes, accompanied by the up-regulation of connexin (Cx)43.
Conclusions
These data indicate that reactivity of drug-resistant prostate cancer cells to metformin may depend on the efficiency of metabolic stress-induced EMT. EMT-related metabolic elasticity that apparently increases invasive potential of PC3 cells in the absence of DCX may limit the application of metformin in therapy of drug-resistant prostate tumors.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
Jagiellonian University, Faculty of Biochemistry, Biophysics and Biotechnology.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.
Resources from the same session
3361 - Providing a nurse-led telephone intervention for patients treated with oral anticancer medication: symptom management and adherence monitoring
Presenter: Etienne Minvielle
Session: Poster Display session 3
Resources:
Abstract
3937 - Chronological evaluation of health-related quality of life and physical symptoms in postoperative pancreatic cancer patients up to 12 months
Presenter: Naoko Sato
Session: Poster Display session 3
Resources:
Abstract
5620 - Understanding the patients’ Experiences of Radiation Therapy: A Qualitative Study on Prostate Cancer Patients
Presenter: Sakarias Johansson
Session: Poster Display session 3
Resources:
Abstract
1792 - Effect of Kegel exercises on prevention of urinary and fecal incontinence in patients with prostate cancer undergoing radiotherapy
Presenter: Aydan Uravylioglu
Session: Poster Display session 3
Resources:
Abstract
2169 - The Meaning of Responsibility – a Secondary Analysis of Patients and Caregivers Calls to an Oncology Emergency Telephone
Presenter: Heidi Jacobsen
Session: Poster Display session 3
Resources:
Abstract
4587 - Cognitive function changes and Associated Factors in Patients Receiving Chemotherapy
Presenter: Elif Dil
Session: Poster Display session 3
Resources:
Abstract
1981 - Prevention of dental complications in patients with multiple myeloma (MM) receiving bisphosphonates treatment
Presenter: CESCA PUIGMARTI
Session: Poster Display session 3
Resources:
Abstract
2725 - Safety profile of oral netupitant/palonosetron in hematopoietic stem cell transplantation recipients.
Presenter: Marina Bosch - Damas
Session: Poster Display session 3
Resources:
Abstract
5112 - Symptomatic and toxicity management of cancer patients using a telephone support model led by the oncology nurse
Presenter: Gemma Simó
Session: Poster Display session 3
Resources:
Abstract
1365 - Symptom cluster of fatigue, sleep disturbance and depression and its impact on quality of life among Chinese breast cancer patients undergoing adjuvant chemotherapy: A cross-sectional study
Presenter: Xiaole HE
Session: Poster Display session 3
Resources:
Abstract