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Wan Youfeng, Xu Yingyi, Zhang Yaya, Chen Yuqiang. Experiment of Anti-OPN Antibody Inhibits Growth and Increases Radiosensitivity of Tumors in Nude Mice Implanted with HCCLM3[J]. Cancer Research on Prevention and Treatment, 2013, 40(03): 240-244. DOI: 10.3971/j.issn.1000-8578.2013.03.005
Citation: Wan Youfeng, Xu Yingyi, Zhang Yaya, Chen Yuqiang. Experiment of Anti-OPN Antibody Inhibits Growth and Increases Radiosensitivity of Tumors in Nude Mice Implanted with HCCLM3[J]. Cancer Research on Prevention and Treatment, 2013, 40(03): 240-244. DOI: 10.3971/j.issn.1000-8578.2013.03.005

Experiment of Anti-OPN Antibody Inhibits Growth and Increases Radiosensitivity of Tumors in Nude Mice Implanted with HCCLM3

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  • Corresponding author:

    Chen Yuqiang:chenyq707@163.com

  • Received Date: April 26, 2012
  • Revised Date: November 27, 2012
  • Objective To study the inhibiting effect of anti-OPN antibodies on tumor growth,metastasis,angiogenesis of HCCLM3 tumor in nude mice and its enhancement effect on radiotherapy. Methods HCCLM3 were inoculated subcutaneously into the right flank of 74 Balb/c nude mice.Next day after inoculation,50 mice were randomized into five groups(10 mice per group):Group A (treatment with normal saline),Group B (treated with non-specific antibody),Group C,D,E (treated with 5 mg/kg,10 mg/kg,20 mg/kg of the anti-OPN antibodies,respectively).The treatments were repeated twice per week and tumor volume was measured every other day. At the end of the 10th week,nude mice killed,tumors and lungs of the mice were collected. Microvessel density (MVD) of tumor tissue was measured by IHC.The other 24 nude mice bearing HCC tumors were randomly divided into four groups:Group F (treated with normal Saline),Group G (treated with 6 MeV electron ray on the tumor),Group H (treated with 20 mg/kg anti-OPN antibody),Group I (treated with 20 mg/kg anti-OPN antibody and 6 MeV electron ray on the tumor).The tumor volume was measured every day and the enhancement factor (EF) was used to evaluate the radiation enhancement. Results Anti-OPN antibody had significant inhibiting effect on the tumor growth (P<0.01),as well as reduced metastasis (P<0.05) and angiogenesis (P<0.05) when comparing with control groups A,B. And among all of them, 20 mg/kg was the most remarkable dose. The inhibition rate of partial tumor growth in combination group I (41.67%),was higher than that of anti-OPN antibody group H (11.86%,P<0.01) and radiation group G(24.04%)(P<0.01). EF>1,which meant anti-OPN antibody had radiotherapy enhancement effect on implented tumor. ConclusionThe anti-OPN antibody can inhibit the tumor growth,metastasis,and angiogenesis and promote the radiotherapy enhancement of liver cancer,which would be another weapon for the HCC.
  • [1]
    Dai J, Li B, Shi J, et al. A humanized anti-osteopontin antibody inhibits breast cancer growth and metastasis in vivo[J]. Cancer Lmmunol Immunother, 2010, 59(3):355-66.
    [2]
    Wang L, Shen ZT, Zhu XX. The radioenhancement effect of gemcitabine on human pancreatic cancer graft in nude mice[J]. Xian Dai Zhong Liu Yi Xue, 2010,18(9):1701-4.[王磊,沈泽天,朱锡旭.吉西他 滨对人胰腺癌裸鼠移植瘤的放疗增敏作用[J]. 现代肿瘤医学,2010,18(9):1701-4.]
    [3]
    Ye QH, Qin LX, Forgues M, et al. Predicting hepatitis B virus-positive metastatic hepatocellular carcinomas using gene expression profiling and supervised machine learning[J]. Nat Med, 2003, 9(4): 416-23.
    [4]
    Weidner N, Semple JP, Welch WR, et al. Tumor angiogenesis and metastasis: correlation in invasive breast carcinoma[J]. N Engl J Med, 1991,324(1):1-8.
    [5]
    Shevde LA, Das S, Clark DW, et al. Osteopontin: an effector and an effect of tumor metastasis[ J]. Curr Mol Med, 2010, 10(1): 71-81.
    [6]
    Rittling SR, Chambers AF. Role of osteopontin in tumor progression[J]. Br J Cancer, 2004, 90 (10): 1877-81.
    [7]
    Wise GE, King GJ. Mechanisms of tooth eruption and orthodontic tooth movement[J]. J Dent Res, 2008, 87(5): 414-34.
    [8]
    Wai PY, Kuo PC. The role of osteopontin in tumor metastasis[J]. J Surg Res, 2004, 121(2):228 -41.
    [9]
    Wang D, You Y, Lin PC, et al. Bcl10 plays a critical role in NF-kappaB activation induced by G protein coupled receptors[J]. Proc Natl Acad Sci U S A, 2007, 104(1):145-50.
    [10]
    Mi Z, Guo H, Wai PY, et al. Integrin 1inked kinase regulates osteopontin-dependent MMP-2 and uPA expression to convey metastatic function in murine mammary epithelial cancer cells[J]. Carcinogenesis, 2006, 27(6): 1134-45.
    [11]
    Zhang H, Ye LH, Zhang XD. Osteopontin(OPN) upregulates calpain small subunit 1(Capn4) Nuclear Facter- B in promotion of hepatoma cell migration[J].Sheng Wu Hua Xue Yu Sheng Wu Wu Li Jin Zhan, 2010,37(5):534-9.[张烜,叶丽虹,张晓东. 骨桥蛋白通过NF- B上调钙蛋白酶小亚基1促进肝癌细胞迁移[J]. 生物化学与生物物理进展,2010,37(5):534-9.]
    [12]
    Zheng J, Hou ZB, Jiao NL. Effects of osteopontin downregulation on the growth of prostate cancer PC-3 cells[J]. Mol Med Report, 2011, 4(6):1225-31.
    [13]
    Yang G, Zhang Y, Wu J, et al. Osteopontin regulates growth and migration of human nasopharyngeal cancer cells[J]. Mol Med Report, 2011, 4(6):1169-73.
    [14]
    Likui W, Hong W, Shuwen Z, et al. The potential of osteopontin as a therapeutic target for human colorectal cancer[J]. J Gastrointest Srug, 2011, 15(4):652-9.
    [15]
    Liu W, Xu G, Ma J, et al. Osteopontin as a key mediator for vasculogenic mimicry in hepatocellular carcinoma[J]. Tohoku J Exp Med, 2011, 224(1):29-39.
    [16]
    Wang HJ, Feng ZQ, Liu YB. Advances in ostenopontin and radiation sensitivity of tumor cells[J ].Sheng Wu Yi Xue Gong Cheng Yu Lin Chuang, 2010, 4(3):271-5.[王海静,冯振卿,刘永彪. 骨桥蛋白与肿 瘤细胞辐射敏感性的研究进展[J]. 生物医学工程与临床, 2010, 4(3):271-5.]
    [17]
    Hahnel A, Wichmann H, Kappler M, et al. Effects of osteopontin inhibition on radiosensitivity of MDA-MB-231 breast cancer cells[J]. Radiat Oncol, 2010, 5:82.
    [18]
    Yang L, Zhao W, Zuo WS, et al. Silencing of osteopontin promotes the radiosensitivity of breast cancer cells by reducing the expression of hypoxia inducible factor 1 and vascular endothelial growth factor[J]. Clin Med J (Engl), 2012, 125(2):293-9.
    [19]
    Solberg TD, Nearman J, Mullins J, et al. Correlation between tumor growth delay and expression of cancer and host VEGF, VEGFR2, and osteopontin in response to radiotherapy[J]. Int J Radiat Oncol Biol Phys, 2008, 72(3):918-26.

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