The Effect and Mechanism of Vascular Endothelial Growth Fac-tor (VEGF) on Tumor Angiogenesis in Gallbladder Carcinoma

  • Dongqing XU Department of Surgery (I), Yiling Hospital of Yichang, Yichang 443100, P.R. China
  • Jianwen LI Department of Surgery (I), Yiling Hospital of Yichang, Yichang 443100, P.R. China
  • Fangfang JIANG Department of Surgery (II), Yiling Hospital of Yichang, Yichang 443100, P.R. China
  • Kaishuang CAI Department of Surgery (I), Yiling Hospital of Yichang, Yichang 443100, P.R. China
  • Guangxue REN Department of Surgery (I), Yiling Hospital of Yichang, Yichang 443100, P.R. China
Keywords: Vascular endothelial growth factor, Gallbladder carcinoma, Angiogenesis, GBC-SD cells, Apoptosis

Abstract

 Background: To investigate the effect of vascular endothelial growth factor (VEGF) on tumor angiogenesis in gallbladder carcinoma. Methods: Fifty one patients with gallbladder carcinoma were enrolled as observation group. Thirty healthy people were included as control group. Chemically synthesized siRNA sequences targeting VEGF was transfected with VEGF-siRNA. A blank group (group B), a negative control group (transfected with independent sequence, group C), and an inhibition group (transfected with VEGF siRNA, group D) were established. Physiological saline was set as group A. The expression of VEGF was detected by qRT-PCR. The expression of VEGF protein was detected by Western blot. MVD was used to measure microvessel density. CCK-8, Transwell and flow cytometry were used to detect cell proliferation, invasion and apoptosis. Results: The tumor volume of nude mice and VEGF mRNA expression in group D was significantly smaller than that in group B and C (P<0.05). The MVD density in group B and C was significantly higher than that in group D (P<0.01). The proliferation of cells was detected from the 3rd day, and the proliferation of cells in the blank and negative control groups was faster than that of the inhibition group (P<0.05). The apoptosis rate of the blank group and the negative control group was lower than that of the inhibition group (P<0.001). Conclusion: VEGF is highly expressed in serum of patients with cholangiocarcinoma, it promotes angiogenesis, proliferation and invasion of gallbladder cancer cells, and inhibits apoptosis of tumor cells.  

References

1. Donohue JH, Stewart AK, Menck HR (1998). The National Cancer Data Base report on carcinoma of the gallbladder, 1989-1995. Cancer, 83: 2618-2628.
2. Ma PX, Zhang R (1999). Synthetic nano-scale fibrous extracellular matrix. J Biomed Mater Res, 46: 60-72.
3. Muething L, Burton JR (2017). Malignancy and Primary Sclerosing Cholangitis: Cholangiocarcinoma, Hepatocellular Car-cinoma, and Gallbladder Carcinoma. Pri-mary Sclerosing Cholangitis. Springer, Cham, 13-27.
4. Martins-Filho ED, Batista TP, Kreimer F, Martins AC, Iwanaga TC, Leao Cde S (2015). Prevalence of incidental gallblad-der cancer in a tertiary-care hospital from pernambuco, Brazil. Arq Gastroenterol, 52: 247-249.
5. Goyal G, Narayan KS, Gupta GK, Nijha-wan S (2017). Carcinoma of gallbladder: Clinical evaluation and survival rate at a tertiary care center in Rajasthan. Indian J Gastroenterol, 36: 326-26.
6. Ferrara N, Adamis AP (2016). Ten years of anti-vascular endothelial growth factor therapy. Nat Rev Drug Discov, 15: 385-403.
7. Zang J, Hu Y, Xu X, Ni J, Yan D, Liu S, He J, Xue J, Wu J, Feng J (2017). Elevated serum levels of vascular endothelial growth factor predict a poor prognosis of platinum-based chemotherapy in non-small cell lung cancer. Onco Targets Ther, 10: 409-415.
8. Zakraoui O, Marcinkiewicz C, Aloui Z et al (2017). Lebein, a snake venom disinteg-rin, suppresses human colon cancer cells proliferation and tumor-induced angio-genesis through cell cycle arrest, apopto-sis induction and inhibition of VEGF expression. Mol Carcinog, 56: 18-35.
9. Giatromanolaki A, Koukourakis MI, Si-mopoulos C, Polychronidis A, Sivridis E (2003). Vascular endothelial growth factor (VEGF) expression in operable gallblad-der carcinomas. Eur J Surg Oncol, 29: 879-883.
10. Jin YP, Hu YP, Wu XS et al (2018). miR-143-3p targeting of ITGA6 suppresses tumour growth and angiogenesis by downregulating PLGF expression via the PI3K/AKT pathway in gallbladder carci-noma. Cell Death Dis, 9: 182.
11. Elbashir SM, Harborth J, Lendeckel W, Yalcin A, Weber K, Tuschl T (2001). Du-plexes of 21-nucleotide RNAs mediate RNA interference in cultured mammalian cells. Nature, 411: 494-498.
12. Chuanliang P, Yunpeng Z, Yingtao H, Qifeng S, Xiaogang Z, Bo C (2016). Syk expression in non-small-cell lung cancer and its relation with angiogenesis. J Cancer Res Ther, 12: 663-666.
13. Meyerhardt JA, Zhu AX, Stuart K et al (2008). Phase-II study of gemcitabine and cisplatin in patients with metastatic biliary and gallbladder cancer. Dig Dis Sci, 53: 564-570.
14. Sun KK, Hu PP, Xu F (2018). Prognostic significance of long non-coding RNA MALAT1 for predicting the recurrence and metastasis of gallbladder cancer and its effect on cell proliferation, migration, invasion, and apoptosis. J Cell Biochem, 119: 3099-3110.
15. McFadden PM, Krementz ET, McKinnon WM, Pararo LL, Ryan RF (1979). Meta-static melanoma of the gallbladder. Cancer, 44: 1802-1808.
16. Picard A, Boscolo E, Khan ZA, Bartch TC, Mulliken JB, Vazquez MP, Bischoff J (2008). IGF-2 and FLT-1/VEGF-R1 mRNA levels reveal distinctions and similarities between congenital and com-mon infantile hemangioma. Pediatr Res, 63: 263-267.
17. Li J, Li L, Li Z, Gong G, Chen P, Liu H, Wang J, Liu Y, Wu X (2015). The role of miR-205 in the VEGF-mediated promotion of human ovarian cancer cell invasion. Gynecol Oncol, 137: 125-133.
18. Kim JH, Kim MS, Lee BH et al (2017). Marmesin-mediated suppression of VEGF/VEGFR and integrin beta1 ex-pression: Its implication in non-small cell lung cancer cell responses and tumor an-giogenesis. Oncol Rep, 37: 91-97.
19. Liu MC, Jiang L, Hong HJ, Meng ZW, Du Q, Zhou LY, She FF, Chen YL (2015). Serum vascular endothelial growth factors C and D as forecast tools for patients with gallbladder carcinoma. Tum Biol, 36: 6305-6312.
20. Liu K, Chen H, You Q, Shi H, Wang Z (2014). The siRNA cocktail targeting VEGF and HER2 inhibition on the pro-liferation and induced apoptosis of gas-tric cancer cell. Mol Cell Biochem, 386: 117-124.
Published
2019-04-17
How to Cite
1.
XU D, LI J, JIANG F, CAI K, REN G. The Effect and Mechanism of Vascular Endothelial Growth Fac-tor (VEGF) on Tumor Angiogenesis in Gallbladder Carcinoma. Iran J Public Health. 48(4):713-721.
Section
Original Article(s)