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
4868 - Evaluation of markers associated with efficacy of abiraterone acetate plus prednisone (AAP) in patients (pts) with castration-sensitive prostate cancer (mCSPC) from the LATITUDE study
Presenter: Kim Chi
Session: Poster Display session 3
Resources:
Abstract
4837 - LRP2, a potential new biomarker for Chinese younger aged intrahepatic cholangiocarcinoma patients
Presenter: Xiaoliang Shi
Session: Poster Display session 3
Resources:
Abstract
1286 - Reanalysis of the efficacy of molecular targeted agents (MTAs) given in the randomized trial SHIVA01 according to the ESMO ESCAT scale of actionability
Presenter: Aurelie Moreira
Session: Poster Display session 3
Resources:
Abstract
2736 - Comparison of Platforms for Determining Tumor Mutational Burden (TMB) From Blood Samples in Patients With Non-Small Cell Lung Cancer (NSCLC)
Presenter: Jonathan Baden
Session: Poster Display session 3
Resources:
Abstract
5045 - Comprehensive Pan-Cancer analysis of somatic mutations in drug transporters to reveal acquired and intrinsic drug resistance in 3149 metastatic cancer patients
Presenter: Sander Bins
Session: Poster Display session 3
Resources:
Abstract
4577 - Pan-Cancer Genomic Landscape of the Cyclin D1/FGF3,4,19 (11q13) Amplicon Including Associations with HPV Status, and ESR1 and AR Alterations
Presenter: Jennifer Johnson
Session: Poster Display session 3
Resources:
Abstract
5366 - Co-occurrence of NTRK fusions with other genomic biomarkers in cancer patients
Presenter: Xiaolong Jiao
Session: Poster Display session 3
Resources:
Abstract
4084 - Prospective comparative study of next-generation sequencing on fine needle aspirations versus core needle biopsies in cancer patients included in SHIVA02 trial
Presenter: Julien Masliah-Planchon
Session: Poster Display session 3
Resources:
Abstract
6017 - First national External Quality Assessement for the interpretation of somatic variants: assessment of 25 variants in colorectal, lung, ovarian cancers and melanoma in France
Presenter: Etienne Rouleau
Session: Poster Display session 3
Resources:
Abstract
2283 - Prospective testing of circulating tumor DNA in metastatic breast cancer facilitates clinical trial enrollment and precision oncology
Presenter: Andjelija Bujak
Session: Poster Display session 3
Resources:
Abstract