Abnormal expression of APRIL in colorectal cancer cells promotes tumor growth and metastasis.
- Author:
Gui-hua WANG
1
;
Mei-hong LU
;
Jing-chun WANG
;
Feng WANG
;
Wei-feng DING
;
Yue-guo WANG
;
Shao-qing JU
;
Hui-min WANG
Author Information
- Publication Type:Journal Article
- MeSH: Animals; Cell Cycle; Cell Line, Tumor; Cell Movement; Cell Proliferation; Colorectal Neoplasms; metabolism; pathology; Cyclin D1; metabolism; Female; Genetic Vectors; HCT116 Cells; HT29 Cells; Humans; Matrix Metalloproteinase 2; metabolism; Matrix Metalloproteinase 9; metabolism; Mice; Mice, Nude; Neoplasm Invasiveness; Neoplasm Metastasis; Neoplasm Transplantation; Plasmids; Proto-Oncogene Proteins c-bcl-2; metabolism; Proto-Oncogene Proteins p21(ras); metabolism; RNA, Messenger; metabolism; RNA, Small Interfering; genetics; Transfection; Tumor Burden; Tumor Necrosis Factor Ligand Superfamily Member 13; genetics; metabolism
- From: Chinese Journal of Oncology 2013;35(4):249-255
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVETo investigate the effects of a proliferation-inducing ligand (APRlL) on colorectal cancer (CRC) cell growth and migration, and to observe the role of APRIL in CRC biological behavior.
METHODSThe siRNA plasmid vector targeting APRIL gene (APRIL-siRNA) was transfected into human colorectal cancer SW480 cells and recombinant human APRIL (rhAPRIL) was used to stimulate human colorectal cancer HCT-116 cells. Cell proliferation activity was analyzed using cell counting kit-8 (CCK-8), cell cycle was detected by flow cytometry, and the protein expression of cyclin D1, p21 and Bcl-2 was detected by Western blot analysis. Tumor cell migration and invasion were measured by Transwell chambers. RT-PCR was applied to examine the mRNA expression level of MMP-2 and MMP-9. APRIL-siRNA was used to transfect directly SW480 cells, which were injected subcutaneously into nude mice, then the tumor growth and metastasis were observed.
RESULTSCell proliferation ability of APRIL-siRNA-transfected SW480 cells was drastically repressed, and the percentage of G0/G1 phase cells was significantly increased (t = 4.12, P < 0.05), accompanied with depressed cyclin D1, Bcl-2 expression and elevated p21 expression. Cell proliferation ability of rhAPRIL-stimulated HCT-116 cells was promoted with a decreased G0/G1 phase ratio (t = 3.31, P < 0.05). cyclin D1 and Bcl-2 protein expression was up-regulated while p21 was down-regulated by rhAPRIL stimulation. Metastatic and invasive capacities of APRIL-siRNA-transfected SW480 cells were significantly inhibited compared with their respective controls (both P < 0.05), accompanied with the deregulated MMP-2 and MMP-9 mRNA expression. Metastatic and invasive capacities of rhAPRIL-stimulated HCT-116 cells were promoted with up-regulated MMP-2 and MMP-9 mRNA expression(both P < 0.05). Tumor growth in the group transfected with APRIL-siRNA appeared to be slower than that in the control groups and the expression of MMP-2, MMP-9 in tumor tissues was depressed in the APRIL-siRNA group.
CONCLUSIONSAPRIL facilitates tumor growth and metastasis, and is associated with carcinogenesis and prognosis. Our findings suggest that APRIL might be used as a novel target for the intervention and therapy of colorectal cancer.
