[Inhibitory effects of an antisense PCDGF vector on proliferation and invasion of highly malignant ovarian cancer cells and the related mechanism].
OBJECTIVE
To investigate the inhibitory effects of an antisense PC cell derived growth factor (PCDGF) vector on proliferation and invasion of highly malignant ovarian cancer cell lines Sw626 and A2780 cells, and preliminarily explore the related mechanisms.


METHODS
MTT assay and Boyden chamber in vitro invasion assay were employed to detect the changes of proliferation and invasion ability in the Sw626 and A2780 cells transfected with anti-sense PCDGF. The expression levels of cyclin D1 and CDK4 proteins before and after transfection were detected by Western blotting. The effects on the expression and activity of MMP-2 were evaluated by quantitative RT-PCR and zymography, respectively.


RESULTS
Comparing with the blank group, the proliferation inhibition rate of the Sw626 and A2780 cells transfected with anti-sense PCDGF was 72.9% and 70.9%, respectively, and the invasion ability was inhibited by 62.9% and 59.0%, respectively. The levels of cyclin D1 and CDK4 protein expression in antisense PCDGF transfected cells were 0.38 +/- 0.08 and 0.37 +/- 0.13, respectively, all significantly lower than 0.84 +/- 0.11 and 0.64 +/- 0.11, respectively, in the blank group (P < 0.01). The MMP-2 mRNA expression level in antisense PCDGF transfected cell group was 0.66 +/- 0.11, not significantly decreased in comparison with 0.89 +/- 0.09 in the blank group (P > 0.05), but the activity of MMP-2 was inhibited significantly.


CONCLUSIONS
The antisense PCDGF vector may inhibit markedly the proliferation and invasion of highly malignant ovarian cancer cells, and partially reverses their malignant phenotype. It seems to be related with down-regulating the expression of cyclin D1 and CDK4 and inhibiting the activity of MMP-2. Our findings indicate that PCDGF may become a new target for antisense gene therapy of ovarian cancer.
Liu
Yu-lan
YL
Department of Gynecology, Hubei Maternal and Child Health Hospital, Wuhan 430070, China.
Wang
Yan
Y
Lang
Yan
Y
Wu
Xu-feng
XF
Xiong
Jun
J
Zhu
Xiao-hong
XH
Zhang
You-hong
YH
Zhang
Shui-juan
SJ
Gong
Li-yan
LY
Lu
Yun-ping
YP
Ma
Ding
D
D002448:Cell Adhesion; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D019938:Cyclin D1 / Q000378:metabolism; D051358:Cyclin-Dependent Kinase 4 / Q000378:metabolism; D016373:DNA, Antisense; D015536:Down-Regulation; D005260:Female; D005822:Genetic Vectors; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D020778:Matrix Metalloproteinase 2 / Q000235:genetics / Q000378:metabolism; D009361:Neoplasm Invasiveness; D010051:Ovarian Neoplasms / Q000378:metabolism / Q000473:pathology*; D000077153:Progranulins; D012333:RNA, Messenger / Q000378:metabolism; D014162:Transfection
D016373:DNA, Antisense; D036341:Intercellular Signaling Peptides and Proteins; D000077153:Progranulins; D012333:RNA, Messenger; D019938:Cyclin D1; C495900:CDK4 protein, human; D051358:Cyclin-Dependent Kinase 4; D020778:Matrix Metalloproteinase 2