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Erschienen in: Tumor Biology 3/2013

01.06.2013 | Research Article

RNAi-mediated gene silencing of vascular endothelial growth factor-C inhibits tumor lymphangiogenesis and growth of gastric cancer in vivo in mice

verfasst von: Jibin Yao, Mingxu Da, Tiankang Guo, Yaoxing Duan, Yongbin Zhang

Erschienen in: Tumor Biology | Ausgabe 3/2013

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Abstract

Overexpression of vascular endothelial growth factor-C (VEGF-C) has been implicated as a critical molecular signal in tumor development by promoting intratumoral lymphangiogenesis. The aim of this study was to explore whether small hairpin RNA (shRNA) targeting VEGF-C could inhibit gastric cancer lymphangiogenesis and tumor growth. Plasmid-mediated expression of VEGF-C–shRNA was employed to silence VEGF-C gene expression in human SGC-7901 cell lines. The inhibition of the target gene expression was quantified by real-time quantitative polymerase chain reaction, Western blotting, and enzyme-linked immunosorbent assay. In vitro, the cell viability was determined by MTT assay, flow cytometry analysis, and migration assay. After VEGF-C knockdown was confirmed, the stable cells were inoculated into nude mice. Tumor growth, lymph vessel density (LVD), and microvascular density were compared for mice administered either VEGF-C–shRNA or control. VEGF-C–shRNA causes effective and specific downregulation of VEGF-C expression (P < 0.05). The migration activity of SGC-7901 cells was attenuated in vitro (P < 0.05). Tumor growth rate and LVD was suppressed in vivo (P < 0.05). VEGF-C–shRNA effectively suppressed gastric cancer cell migration in vivo, retards tumorigenicity, and lymphangiogenesis in nude mice.
Literatur
4.
Zurück zum Zitat Lordick F, Schumacher G, Becker-Schiebe M. Gastric cancer—still many questions to be solved. MEMO. 2011;4(2):71–4.CrossRef Lordick F, Schumacher G, Becker-Schiebe M. Gastric cancer—still many questions to be solved. MEMO. 2011;4(2):71–4.CrossRef
7.
Zurück zum Zitat Nagahashi M, Ramachandran S, Rashid OM, Takabe K. Lymphangiogenesis: a new player in cancer progression. World J Gastroenterol. 2010;16(32):4003–12.PubMedCrossRef Nagahashi M, Ramachandran S, Rashid OM, Takabe K. Lymphangiogenesis: a new player in cancer progression. World J Gastroenterol. 2010;16(32):4003–12.PubMedCrossRef
10.
Zurück zum Zitat Tsutsumi S, Kuwano H, Shimura T, Morinaga N, Mochiki E, Asao T. Vascular endothelial growth factor C (VEGF-C) expression in pT2 gastric cancer. Hepatogastroenterology. 2005;52(62):629–32.PubMed Tsutsumi S, Kuwano H, Shimura T, Morinaga N, Mochiki E, Asao T. Vascular endothelial growth factor C (VEGF-C) expression in pT2 gastric cancer. Hepatogastroenterology. 2005;52(62):629–32.PubMed
11.
Zurück zum Zitat Karpanen T, Egeblad M, Karkkainen MJ, Kubo H, Yla-Herttuala S, Jaattela M, et al. Vascular endothelial growth factor C promotes tumor lymphangiogenesis and intralymphatic tumor growth. Cancer Res. 2001;61(5):1786–90.PubMed Karpanen T, Egeblad M, Karkkainen MJ, Kubo H, Yla-Herttuala S, Jaattela M, et al. Vascular endothelial growth factor C promotes tumor lymphangiogenesis and intralymphatic tumor growth. Cancer Res. 2001;61(5):1786–90.PubMed
12.
Zurück zum Zitat Shi X, Chen G, Xing H, Weng D, Bai X, Ma D. VEGF-C, VEGFR-3, and COX-2 enhances growth and metastasis of human cervical carcinoma cell lines in vitro. Oncol Rep. 2007;18(1):241–7.PubMed Shi X, Chen G, Xing H, Weng D, Bai X, Ma D. VEGF-C, VEGFR-3, and COX-2 enhances growth and metastasis of human cervical carcinoma cell lines in vitro. Oncol Rep. 2007;18(1):241–7.PubMed
13.
Zurück zum Zitat Ochi N, Matsuo Y, Sawai H, Yasuda A, Takahashi H, Sato M, et al. Vascular endothelial growth factor-C secreted by pancreatic cancer cell line promotes lymphatic endothelial cell migration in an in vitro model of tumor lymphangiogenesis. Pancreas. 2007;34(4):444–51.PubMedCrossRef Ochi N, Matsuo Y, Sawai H, Yasuda A, Takahashi H, Sato M, et al. Vascular endothelial growth factor-C secreted by pancreatic cancer cell line promotes lymphatic endothelial cell migration in an in vitro model of tumor lymphangiogenesis. Pancreas. 2007;34(4):444–51.PubMedCrossRef
14.
Zurück zum Zitat Morita H, Ishikawa Y, Akishima-Fukasawa Y, Ito K, Akasaka Y, Nishimura C, et al. Histopathological predictor for regional lymph node metastasis in gastric cancer. Virchows Arch. 2009;454(2):143–51. doi:10.1007/s00428-008-0717-3.PubMedCrossRef Morita H, Ishikawa Y, Akishima-Fukasawa Y, Ito K, Akasaka Y, Nishimura C, et al. Histopathological predictor for regional lymph node metastasis in gastric cancer. Virchows Arch. 2009;454(2):143–51. doi:10.​1007/​s00428-008-0717-3.PubMedCrossRef
16.
Zurück zum Zitat Schoppmann S, Fenzl A, Schindl M, Bachleitner-Hofmann T, Nagy K, Gnant M, et al. Hypoxia inducible factor-1α correlates with VEGF-C expression and lymphangiogenesis in breast cancer. Breast Cancer Res Tr. 2006;99(2):135–41. doi:10.1007/s10549-006-9190-3.CrossRef Schoppmann S, Fenzl A, Schindl M, Bachleitner-Hofmann T, Nagy K, Gnant M, et al. Hypoxia inducible factor-1α correlates with VEGF-C expression and lymphangiogenesis in breast cancer. Breast Cancer Res Tr. 2006;99(2):135–41. doi:10.​1007/​s10549-006-9190-3.CrossRef
17.
Zurück zum Zitat Dias S, Choy M, Alitalo K, Rafii S. Vascular endothelial growth factor (VEGF)-C signaling through FLT-4 (VEGFR-3) mediates leukemic cell proliferation, survival, and resistance to chemotherapy. Blood. 2002;99(6):2179–84.PubMedCrossRef Dias S, Choy M, Alitalo K, Rafii S. Vascular endothelial growth factor (VEGF)-C signaling through FLT-4 (VEGFR-3) mediates leukemic cell proliferation, survival, and resistance to chemotherapy. Blood. 2002;99(6):2179–84.PubMedCrossRef
20.
21.
Zurück zum Zitat Harborth J, Elbashir SM, Bechert K, Tuschl T, Weber K. Identification of essential genes in cultured mammalian cells using small interfering RNAs. J Cell Sci. 2001;114(24):4557–65.PubMed Harborth J, Elbashir SM, Bechert K, Tuschl T, Weber K. Identification of essential genes in cultured mammalian cells using small interfering RNAs. J Cell Sci. 2001;114(24):4557–65.PubMed
22.
23.
Zurück zum Zitat Yu JY, DeRuiter SL, Turner DL. RNA interference by expression of short-interfering RNAs and hairpin RNAs in mammalian cells. Proc Natl Acad Sci USA. 2002;99(9):6047–52.PubMedCrossRef Yu JY, DeRuiter SL, Turner DL. RNA interference by expression of short-interfering RNAs and hairpin RNAs in mammalian cells. Proc Natl Acad Sci USA. 2002;99(9):6047–52.PubMedCrossRef
25.
26.
Zurück zum Zitat Enholm B, Paavonen K, Ristimäki A, Kumar V, Gunji Y, Klefstrom J, et al. Comparison of VEGF, VEGF-B, VEGF-C and Ang-1 mRNA regulation by serum, growth factors, oncoproteins and hypoxia. Oncogene. 1997;14(20):2475–83.PubMedCrossRef Enholm B, Paavonen K, Ristimäki A, Kumar V, Gunji Y, Klefstrom J, et al. Comparison of VEGF, VEGF-B, VEGF-C and Ang-1 mRNA regulation by serum, growth factors, oncoproteins and hypoxia. Oncogene. 1997;14(20):2475–83.PubMedCrossRef
27.
Zurück zum Zitat Li H, Adachi Y, Yamamoto H, Min Y, Ohashi H, Ii M, et al. Insulin-like growth factor-I receptor blockade reduces tumor angiogenesis and enhances the effects of bevacizumab for a human gastric cancer cell line, MKN45. Cancer. 2011;117(14):3135–47. doi:10.1002/cncr.25893.PubMedCrossRef Li H, Adachi Y, Yamamoto H, Min Y, Ohashi H, Ii M, et al. Insulin-like growth factor-I receptor blockade reduces tumor angiogenesis and enhances the effects of bevacizumab for a human gastric cancer cell line, MKN45. Cancer. 2011;117(14):3135–47. doi:10.​1002/​cncr.​25893.PubMedCrossRef
33.
Zurück zum Zitat He M, Cheng Y, Li W, Liu QS, Liu JX, Huang JH, et al. Vascular endothelial growth factor C promotes cervical cancer metastasis via up-regulation and activation of RhoA/ROCK-2/moesin cascade. Cancer. 2010;10:1710. doi:10.1186/1471-2407-10-170. He M, Cheng Y, Li W, Liu QS, Liu JX, Huang JH, et al. Vascular endothelial growth factor C promotes cervical cancer metastasis via up-regulation and activation of RhoA/ROCK-2/moesin cascade. Cancer. 2010;10:1710. doi:10.​1186/​1471-2407-10-170.
36.
Zurück zum Zitat Guo BL, Zhang YF, Luo GQ, Li LC, Zhang JG. Lentivirus-mediated small interfering RNA targeting VEGF-C inhibited tumor lymphangiogenesis and growth in breast carcinoma. Anat Rec Adv Integr Anat Evol Biol. 2009;292(5):633–9. doi:10.1002/ar.20893.CrossRef Guo BL, Zhang YF, Luo GQ, Li LC, Zhang JG. Lentivirus-mediated small interfering RNA targeting VEGF-C inhibited tumor lymphangiogenesis and growth in breast carcinoma. Anat Rec Adv Integr Anat Evol Biol. 2009;292(5):633–9. doi:10.​1002/​ar.​20893.CrossRef
Metadaten
Titel
RNAi-mediated gene silencing of vascular endothelial growth factor-C inhibits tumor lymphangiogenesis and growth of gastric cancer in vivo in mice
verfasst von
Jibin Yao
Mingxu Da
Tiankang Guo
Yaoxing Duan
Yongbin Zhang
Publikationsdatum
01.06.2013
Verlag
Springer Netherlands
Erschienen in
Tumor Biology / Ausgabe 3/2013
Print ISSN: 1010-4283
Elektronische ISSN: 1423-0380
DOI
https://doi.org/10.1007/s13277-013-0674-6

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