A1 Vertaisarvioitu alkuperäisartikkeli tieteellisessä lehdessä
Cediranib, an inhibitor of vascular endothelial growth factor receptor kinases, inhibits proliferation and invasion of prostate adenocarcinoma cells
Tekijät: Majid Momeny, Ghazaleh Sankanian, Sepideh Hamzehlou, Hassan Yousefi, Fatemeh Esmaeili, Zivar Alishahi, Behnaz Karimi, Zahra Zandi, Sahar Shamsaiegahkani, Zahra Sabourinejad, Bahareh Kashani, Ali Nasrollahzadeh, Seyyedeh H.Mousavipak, Seyed A. Mousavi, Seyed H. Ghaffari
Kustantaja: ELSEVIER
Julkaisuvuosi: 2020
Journal: European Journal of Pharmacology
Tietokannassa oleva lehden nimi: EUROPEAN JOURNAL OF PHARMACOLOGY
Lehden akronyymi: EUR J PHARMACOL
Artikkelin numero: ARTN 173298
Vuosikerta: 882
Sivujen määrä: 9
ISSN: 0014-2999
eISSN: 1879-0712
DOI: https://doi.org/10.1016/j.ejphar.2020.173298
Prostate Cancer is the second cause of cancer-related death in men and development of metastatic castration-resistant prostate cancer (mCRPC) is the major reason for its high mortality rate. Despite various treatments, all patients succumb to resistant disease, suggesting that there is a pressing need for novel and more efficacious treatments. Members of the vascular endothelial growth factor (VEGF) family play key roles in the tumorigenesis of mCRPC, indicating that VEGF-targeted therapies may have potential anti-tumor efficacy in this malignancy. However, due to compensatory activation of other family members, clinical trials with single-targeted VEGF inhibitors were discouraging. Here, we determined the anti-neoplastic activity of Cediranib, a pan-VEGF receptor inhibitor, in the mCRPC cell lines.Anti-growth effects of Cediranib were studied by MTT and BrdU cell proliferation assays and crystal violet staining. Annexin V/PI, radiation therapy and cell motility assays were carried out to examine the effects of Cediranib on apoptosis, radio-sensitivity and cell motility. Quantitative reverse transcription-PCR (qRT-PCR) and Western blot analyses were conducted to determine the molecular mechanisms underlying the anti-tumor activity of Cediranib.Cediranib decreased cell viability and induced apoptosis via inhibition of the anti-apoptotic proteins. Combination with Cediranib synergistically increased Docetaxel sensitivity and potentiated the effects of radiation therapy. Furthermore, Cediranib impaired cell motility via decrease in the expression of the epithelial-to-mesenchymal transition markers. These findings suggest that Cediranib may have anti-tumor activity in mCRPC cells and warrant further investigation on the therapeutic activity of this pan-VEGF receptor inhibitor in mCRPC.
