Author/Authors :
Fanian, Maryam Diagnostic Laboratory Sciences and Technology Research Center - School of Paramedical Sciences - Shiraz University of Medical Sciences, Shiraz, Iran , Bahmani, Maedeh Department of Biotechnology - School of Pharmacy - Shiraz University of Medical Sciences, Shiraz, Iran , Mozafari, Mojdeh Department of Biotechnology - School of Pharmacy - Shiraz University of Medical Sciences, Shiraz, Iran , Naderi, Samaneh Diagnostic Laboratory Sciences and Technology Research Center - School of Paramedical Sciences - Shiraz University of Medical Sciences, Shiraz, Iran , Alizadeh Zareie, Marzieh Diagnostic Laboratory Sciences and Technology Research Center - School of Paramedical Sciences - Shiraz University of Medical Sciences, Shiraz, Iran , Okhovat, Mohammad Ali Diagnostic Laboratory Sciences and Technology Research Center - School of Paramedical Sciences - Shiraz University of Medical Sciences, Shiraz, Iran , Saberzadeh, Jamileh Diagnostic Laboratory Sciences and Technology Research Center - School of Paramedical Sciences - Shiraz University of Medical Sciences, Shiraz, Iran , Dehshahri, Ali Department of Biotechnology - School of Pharmacy - Shiraz University of Medical Sciences, Shiraz, Iran , Takhshid, Mohammad Ali Diagnostic Laboratory Sciences and Technology Research Center - School of Paramedical Sciences - Shiraz University of Medical Sciences, Shiraz, Iran
Abstract :
Metastasis to lymph nodes and distant organs is the main challenge in the treatment of
papillary thyroid cancer. In the current investigation, we aimed to evaluate the synergistic effects
of celecoxib (CX) and sodium valproate (VPA) against cell survival, invasiveness properties,
and expression of metalloproteinase-2 and -9 (MMP-2 and MMP-9) in papillary thyroid cancer
cell line, B-CPAP cells. The effect of CX and VPA on B-CPAP cells viability and apoptosis
were investigated using MTT assay and annexin V/7-AAD flowcytometry, respectively. The
effects of the drugs on invasiveness properties of B-CPAP cells and expression of MMP-2 and
MMP-9 were evaluated using transwell assay and real time PCR, respectively. MTT assay
showed that CX and VPA decreased viability of B-CPAP cells dose dependently (IC50 32.4μM
and 6.8 mM, respectively). Combination of CX (5 μM) and VPA (2.5 and 5 mM) increased
apoptosis, and reduced cell migration and invasion of B-CPAP cell, synergistically. Real time
PCR results showed that both CX (5 μM) and VPA (2.5 and 5 mM) reduced MMP-2 expression
(P < 0.05) but had no significant effects on the expression of MMP-9. Our findings suggest
that CX and VPA synergistically increase apoptosis and suppress migration and invasion of
B-CPAP cells through inhibition of MMP-2 expression.
Keywords :
Sodium Valproate , Celecoxib , Migration , Invasion , Apoptosis , Papillary thyroid cancer
