Inhibition of AGS Cancer Cell Proliferation following siRNA-Mediated Downregulation of VEGFR2.
OBJECTIVE
Vascular endothelial growth factor (VEGF) and VEGF receptors (VEGFRs) play important roles in angiogenesis of different developmental mechanisms such as wound healing, embryogenesis and diseases, including different types of cancer. VEGFR2 is associated with cell proliferation, migration, and vascular permeability of endothelial cells. Blocking VEGF and its receptors is suggested as a therapeutic approach to prevent tumor growth. In this study, we aim to block VEGF signaling via small interfering RNA (siRNA) inhibition of VEGFR2.


METHODS
In this experimental study, we used the RNA interference (RNAi) mechanism to suppress expression of the VEGFR2 gene. We conducted the 3-(4,5-di- methylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide (MTT) assay, real-time polymerase chain reaction (PCR), Western blot, and flow cytometry analyses of VEGFR2 expression.


RESULTS
Real-time PCR and Western blot results showed that VEGFR2 expression significantly downregulated. This suppression was followed by inhibition of cell prolifera- tion, reduction of viability, and induction of apoptosis in the cancer cells.


CONCLUSIONS
These findings suggest that VEGFR2 has a role in cell proliferation and tumor growth. Accordingly, it is suggested that VEGFR2 can be a therapeutic target for controlling tumor growth and proliferation.
Department of Biochemical, Chemical Injuries Research Center, Baqiyatallah University of Medical Science, Tehran, Iran.
Ali
A
Zarei Mahmudabadi
Department of Immunology, Faculty of Medicine, Torbat Heydariyeh University of Medical Sciences, Torbat Heydariyeh, Iran.
Masoomeh
M
Masoomi Karimi
Department of Biochemistry, Qazvin University of Medical Sciences, Qazvin, Iran.
Majid
M
Bahabadi
Department of Biochemistry, Rafsanjan University of Medical Sciences, Rafsanjan, Iran.
Zahra
Z
Bagheri Hoseinabadi
Department of Basic Sciences, School of Medicine, Shahroud University of Medical Sciences, Shahroud, Iran.
Moslem
M
JafariSani
Biochemistry Center, Shahrekord University of Medical Sciences, Shahrekord, Iran.
Reza
R
Ahmadi
Apoptosis; Downregulation; VEGFR2; siRNA