Abstract 2779
Background
Pancreatic ductal adenocarcinoma (PDAC) is the most common and lethal subtype of pancreatic cancer, with a 5-year survival rate of less than 3%. Early tumor dissemination, late diagnosis, and insensitivity to conventional treatments are the major reasons for its high mortality rate. Members of vascular endothelial growth factor (VEGF) family are overexpressed in PDAC and play important roles in its malignant progression, suggesting that VEGF-targeted therapies are potentially promising to interrupt proliferation and motility of PDAC cells. Here, we evaluated the anti-tumor activity of cediranib, a pan-VEGF receptor inhibitor, on PDAC cells.
Methods
Anti-proliferative effects of cediranib were determined using cell proliferation assay and crystal violet staining. Annexin V/PI staining, radiation therapy and cell migration and invasion assays were carried out to examine the effects of cediranib on apoptosis, radiosensitivity, and cell motility, respectively. Quantitative reverse transcription-PCR (qRT-PCR) and Western blot analysis were applied to elucidate the molecular mechanisms for the anti-tumor activity of cediranib.
Results
Cediranib hindered cell proliferation and clonogenic survival and induced apoptotic cell death through inhibition of the anti-apoptotic proteins cIAP1, XIAP, MCL-1, and survivin. Combination with cediranib synergistically increased sensitivity to the chemotherapeutic agents gemcitabine and paclitaxel and potentiated the effects of radiation therapy on inhibition of cell growth and induction of apoptosis. Furthermore, treatment with cediranib impaired PDAC cell migration and invasion via reduction of epithelial-to-mesenchymal transition (EMT) markers ZEB1, N-cadherin and Snail.
Conclusions
These findings suggest that cediranib has potential anti-tumor activity in the PDAC cells and provide a rationale for further investigation on the therapeutic potential of this VEGFR-targeted therapy in the treatment of PDAC.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Hematology/Oncology and Stem Cell Transplantation Research Center, Tehran University of Medical Sciences, Tehran, Iran.
Disclosure
All authors have declared no conflicts of interest.
Resources from the same session
2344 - Lung Cancer in Europe: strengthening policy responses to address unmet needs
Presenter: Mary Bussell
Session: Poster Display session 3
Resources:
Abstract
1359 - Curative treatment timelines for breast, colorectal, lung and prostate cancer: Implications for medical leave coverage
Presenter: Selina Wong
Session: Poster Display session 3
Resources:
Abstract
4433 - Acute Diagnostic Oncology Clinic: A Unique Primary Care-Oncology Service
Presenter: Abhijit Gill
Session: Poster Display session 3
Resources:
Abstract
3506 - THE NEW MUTATIONAL MODEL IN ONCOLOGY. What changes in welfare, clinical practice, research, and regulatory procedures
Presenter: Nicola Normanno
Session: Poster Display session 3
Resources:
Abstract
3350 - Selection of a set of quality indicators (QI) for oncological clinical pathway
Presenter: Aude Fourcade
Session: Poster Display session 3
Resources:
Abstract
4400 - Sustainable drug prices at market launch: policy proposals and their empirical evidence
Presenter: Nora Fanzen
Session: Poster Display session 3
Resources:
Abstract
4118 - Impact of financial considerations on French physicians’ prescription choices for advanced non-small cell lung cancer (NSCLC)
Presenter: Nathalie Olympios
Session: Poster Display session 3
Resources:
Abstract
1340 - The direct medical cost of breast cancer in a Belgian hospital
Presenter: Hannan Lemhouer
Session: Poster Display session 3
Resources:
Abstract
1863 - Does the healthcare system approaches cancer patients for using private services during diagnostic process?
Presenter: Karolina Osowiecka
Session: Poster Display session 3
Resources:
Abstract
2637 - Measuring financial toxicity of cancer in the Italian health care system: initial results of the patient reported outcome for Fighting Financial Toxicity of cancer project (proFFiT).
Presenter: Silvia Riva
Session: Poster Display session 3
Resources:
Abstract