The influence of lentivirus-mediated CXCR4 RNA interference on hepatic metastasis of colorectal cancer

被引:13
作者
Wang, Tian-Bao [1 ]
Hu, Bao-Guang [3 ]
Liu, Da-Wei [2 ]
Shi, Han-Ping [1 ]
Dong, Wen-Guang [1 ]
机构
[1] Sun Yat Sen Univ, Affiliated Hosp 1, Dept Surg, Guangzhou 510080, Guangdong, Peoples R China
[2] Sun Yat Sen Univ, Affiliated Hosp 1, Dept Pathol, Guangzhou 510080, Guangdong, Peoples R China
[3] Chinese Univ Hong Kong, Prince Wales Hosp, Dept Surg, Shatin, Hong Kong, Peoples R China
关键词
CXCR4; RNA interference; lentivirus; SW480; cell; hepatic metastasis; CHEMOKINE RECEPTOR CXCR4; LYMPH-NODE METASTASIS; TARGETING CXCR4; POOR-PROGNOSIS; BREAST-CANCER; CELL-LINES; INVASION; EXPRESSION; MIGRATION; GROWTH;
D O I
10.3892/ijo.2014.2348
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
The aim of this study was to construct a lentiviral vector of CXCR4-siRNA (Lenti-CXCR4-siRNA) and investigate whether the vector can inhibit the growth, migration, invasion and hepatic metastasis of colorectal cancer (CRC). RT-PCR and western blotting were employed to identify the ideal RNA interference sequence. Lenti-CXCR4-siRNA was constructed and transfected into the SW480 cell line. We used RT-PCR and western blotting to measure the expression of CXCR4 RNA and protein, respectively; the MTS assay to assess the proliferation of SW480 cells; transwell chambers to estimate the inhibitory effect on migration and invasion; and the Balb/c nude mouse model of CRC to examine the inhibition of hepatic metastasis. The relative expression of the CXCR4 gene and protein was 5.4 and 18.95%, respectively, in the siCXCR4 group. The genes in the expression plasmid pLenti-CXCR4-siRNA were in the correct order. In the SW480, nonsense control (NC) and the Lenti-CXCR4-siRNA groups CXCR4 RNA levels were, respectively, 0.54 +/- 0.06, 1.00 +/- 0.03 and 0.11 +/- 0.04 (P=0.0001); CXCR4 protein levels were 0.60 +/- 0.03, 0.72 +/- 0.03 and 0.18 +/- 0.02 (P=0.0001); the OD value was 1.38 +/- 0.04 (P=0.0050), 1.28 +/- 0.05 (P=0.0256) and 0.92 +/- 0.06; SW480 cell number in migration test was 32 +/- 6.85, 32.63 +/- 1.69 and 0.75 +/- 0.71 (P=0.0000); SW480 cell number in the invasion test was 29.13 +/- 10.3, 30.38 +/- 6.09 and 0.63 +/- 0.74 (P=0.0000); hepatic metastasis number was 7.10 +/- 3.98 (P=0.034), 7.50 +/- 4.09 (P=0.019) and (3.50 +/- 2.51); hepatic metastasis mean weight (in g) was 2.25 +/- 2.51 (P=0.000), 2.11 +/- 2.38 (P=0.000) and 1.45 +/- 2.07. Lenti-CXCR4-siRNA constructs were correctly constructed and effectively inhibit the expression of CXCR4 RNA and protein, reducing the proliferation, migration, invasion capacity of SW480 cells and hepatic metastasis of CRC.
引用
收藏
页码:1861 / 1869
页数:9
相关论文
共 44 条
[1]   Cancer and the chemokine network [J].
Balkwill, F .
NATURE REVIEWS CANCER, 2004, 4 (07) :540-550
[2]   CXCR4 and CXCL12 are inversely expressed in colorectal cancer cells and modulate cancer cell migration, invasion and MMP-9 activation [J].
Brand, S ;
Dambacher, J ;
Beigel, F ;
Olszak, T ;
Diebold, J ;
Otte, JM ;
Göke, B ;
Eichhorst, ST .
EXPERIMENTAL CELL RESEARCH, 2005, 310 (01) :117-130
[3]   CXCR4/CXCL12 in Non-Small-Cell Lung Cancer Metastasis to the Brain [J].
Cavallaro, Sebastiano .
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, 2013, 14 (01) :1713-1727
[4]   Antitumor Effects of Targeting hTERT Lentivirus-Mediated RNA Interference Against KB Cell Lines [J].
Chen, Dan ;
Huang, Hongzhang ;
Pan, Chaobin ;
Wang, Jianguang ;
Zhang, Bin ;
Wang, Anxun .
ONCOLOGY RESEARCH, 2009, 17 (11-12) :621-630
[5]   Biological role and potential therapeutic targeting of the chemokine receptor CXCR4 in undifferentiated thyroid cancer [J].
De Falco, Valentina ;
Guarino, Valentina ;
Avilla, Elvira ;
Castellone, Maria Domenica ;
Salerno, Paolo ;
Salvatore, Giuliana ;
Faviana, Pinuccia ;
Basolo, Fulvio ;
Santoro, Massimo ;
Melillo, Rosa Marina .
CANCER RESEARCH, 2007, 67 (24) :11821-11829
[6]   met oncogene activation qualifies spontaneous canine osteosarcoma as a suitable pre-clinical model of human osteosarcoma [J].
De Maria, Raffaella ;
Miretti, Silvia ;
Iussich, Selina ;
Olivero, Martina ;
Morello, Emanuela ;
Bertotti, Andrea ;
Christensen, James G. ;
Biolatti, Bartolomeo ;
Levine, Roy A. ;
Buracco, Paolo ;
Di Renzo, Maria Flavia .
JOURNAL OF PATHOLOGY, 2009, 218 (03) :399-408
[7]   Association between expression of vascular endothelial growth factor c, chemokine receptor CXCR4 and lymph node metastasis in colorectal cancer [J].
Fukunaga, S. ;
Maeda, K. ;
Noda, E. ;
Inoue, T. ;
Wada, K. ;
Hirakawa, K. .
ONCOLOGY, 2006, 71 (3-4) :204-211
[8]   Involvement of CXCR4 Chemokine Receptor in Metastastic HER2-Positive Esophageal Cancer [J].
Gros, Stephanie J. ;
Kurschat, Nina ;
Drenckhan, Astrid ;
Dohrmann, Thorsten ;
Forberich, Evelyn ;
Effenberger, Katharina ;
Reichelt, Uta ;
Hoffman, Robert M. ;
Pantel, Klaus ;
Kaifi, Jussuf T. ;
Izbicki, Jakob R. .
PLOS ONE, 2012, 7 (10)
[9]   A Lentiviral CXCR4 Overexpression and Knockdown Model in Colorectal Cancer Cell Lines Reveals Plerixafor-Dependent Suppression of SDF-1α-Induced Migration and Invasion [J].
Heckmann, Doreen ;
Laufs, Stephanie ;
Maier, Patrick ;
Zucknick, Manuela ;
Giordano, Frank A. ;
Veldwijk, Marlon R. ;
Eckstein, Volker ;
Wenz, Frederik ;
Zeller, W. Jens ;
Fruehauf, Stefan ;
Allgayer, Heike .
ONKOLOGIE, 2011, 34 (10) :502-508
[10]   Correlation between Chemokine Receptor CXCR4 Expression and Prognostic Factors in Patients with Prostate Cancer [J].
Jung, Seok Jin ;
Kim, Chun Il ;
Park, Choal Hee ;
Chang, Hyuk Soo ;
Kim, Byung Hoon ;
Choi, Mi Sun ;
Jung, Hyea Ra .
KOREAN JOURNAL OF UROLOGY, 2011, 52 (09) :607-611