Effects Of VEGF-C Antisense Oligodeoxynucleotide On The Biological Behavior Of Human Ovarian Cancer SKOV3 Cell Line

Objective: To investigate the effects of VEGF-C antisense oligodeoxynucleotide on the biological behavior of ovarian cancer cell line SKOV3.Methods: Phosphorothioate VEGF-C ASODN were synthesized and transfected to SKOV3 cells mediated by lipofectin. The cell proliferation was detected by MTT and the cell morphological change was observed under microscope;The cell cycle was dectected by flow cytometry;The expression of VEGF-C protein was detected by S-P immunocytochemical technique;The adhesion of SKOV3 cells to artifical basement membrane Matrigel was measured by MTT; The invasion and migration was evaluated by transwell chambers;The expression level of E-cadherin and MMP-2 protein was measured by Western-blot.Results: 1.VEGF-C ASODN could significantly inhibit the growth of SKOV3 cells(P<0.01) in a dose-and time-dependent manner while the LF control group and SODN groups showed no effect. 2.VEGF-C ASODN could induce cell apoptosis, typical features of apoptosis such as pyknosis and karyorrhexis could be found under microscope. 3.Flow cytometry analysis showed that in VEGF-C ASODN group the cell apoptosis rate was 14.55% and the cell percentage in S phase increased than the control and SODN groups, cells were arrested in S phase. 4.The immunocytochemistry method indicated that the expression of VEGF-C protein was downregulated remarkably by VEGF-C ASODN than the than the control and SODN groups(P<0.01). 5.The result of adhesion experiment demonstrated that VEGF-C ASODN could suppress the adhesion ability of SKOV3 cells to Matrigel obviously at 30min,60min,90min and 120min compared with the control and SODN group(sP<0.01). 6.The invasive and metastatic cell numbers in VEGF-C ASODN group decreased significantly than the control and SODN groups(P<0.01). 7.The result of Western-blot showed the expression of E-cadherin protein was up-regulated remarkably and the expression of MMP-2 protein was down-regulated obviously compared with the control and SODN groups(P<0.01).Conclusions: VEGF-C ASODN could inhibit the proliferation and the invasion and metastasis of SKOV3 cells remarkably and could provide an effective adjunctive therapy for ovarian cancer.