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Article

G31P, CXCR1/2 inhibitor, with cisplatin inhibits the growth of mice hepatocellular carcinoma and mitigates high‑dose cisplatin-induced nephrotoxicity

  • Authors:
    • Lingyun Li
    • Muhammad Noman Khan
    • Qiang Li
    • Xiangyu Chen
    • Jing Wei
    • Bing Wang
    • Jya-Wei Cheng
    • John R. Gordon
    • Fang Li
  • View Affiliations / Copyright

    Affiliations: Department of Immunology, Dalian Medical University, Dalian, Liaoning 116044, P.R. China, Jilin Medical College, Jilin 132013, P.R. China, Department of Immunology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, P.R. China, Institute of Biotechnology, Department of Life Science, National Tsing Hua University, Hsinchu 300, Taiwan, R.O.C., The Division of Respirology, Critical Care and Sleep Medicine, Royal University Hospital, University of Saskatchewan, Saskatoon, SK S7N 0W8, Canada
  • Pages: 751-757
    |
    Published online on: December 8, 2014
       https://doi.org/10.3892/or.2014.3659
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Abstract

Cisplatin (DDP), a cytotoxic antitumor drug, functions in a dose-dependent manner. However, the pursuit for high‑dose therapeutic effects leads to more serious side effects including kidney toxicity. Nephrotoxicity caused due to endothelial cell dysfunction and neutrophils infiltration in kidneys. Interleukin-8 (IL-8) is an ELR+ chemokine binds with CXCR1/2 receptors and its role is primarily in neutrophils recruitment and also involved in invasion, angiogenesis and metastasis of different solid tumors including liver cancer. G31P, a CXCR1/2 antagonist, binds with CXCR1/2 with high affinity, and acts as an anti-inflammatory and antitumor agent. In the present study, we examined the antitumor effects of G31P and DDP on mouse liver cancer cells, and the effects exerted by G31P on cisplatin-induced renal injury. In vitro, effects of the G31P and DDP regimen on H22 cell proliferation were investigated by MTT assay. In vivo BALB/c mice were inoculated subcutaneously with 1x106 H22 cells and treated after one week with a high single dose of DDP with and without G31P on alternative days until the experiment was terminated. On the 15th day the mice were sacrificed, dissected and kidney tissues were analyzed using H&E staining. Myeloperoxidase (MPO) activity was assessed and RT-PCR was performed to detect inflammatory cytokines. Solid tumors were weighed for tumor growth and performed pathological examination, immunohistochemistry and western blotting were performed to detect tissue-related protein expressions in tumor tissue. The tumor inhibitory rate of DDP, G31P and DDP+G31P groups was 38.40, 40.74 and 74.80%, respectively, and the general state of mice in the DDP+G31P group was significantly improved as compared to the DDP group. The results indicated that G31P with DDP significantly inhibited the proliferation while the growth of H22 cell carnimona in vitro and in vivo enhanced the efficacy of cisplatin in cancer treatment with reduced side effects on acute renal failure.
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1 

Forner A, Llovet JM and Bruix J: Hepatocellular carcinoma. Lancet. 379:1245–1255. 2012. View Article : Google Scholar : PubMed/NCBI

2 

Shen FZ, Wang J, Liang J, Mu K, Hou JY and Wang YT: Low-dose metronomic chemotherapy with cisplatin: can it suppress angiogenesis in H22 hepatocarcinoma cells? Int J Exp Pathol. 91:10–16. 2010. View Article : Google Scholar : PubMed/NCBI

3 

Ozdogan O, Ertay T, Arslan G, et al: Does cisplatin chemotherapy decrease the MDP uptake of normal bone? An experimental study. Ann Nucl Med. 22:357–362. 2008. View Article : Google Scholar : PubMed/NCBI

4 

Arany I and Safirstein RL: Cisplatin nephrotoxicity. Semin Nephrol. 23:460–464. 2003. View Article : Google Scholar : PubMed/NCBI

5 

Bonventre JV: Pathophysiology of ischemic acute renal failure. Inflammation, lung-kidney cross-talk, and biomarkers. Contrib Nephrol. 144:19–30. 2004. View Article : Google Scholar : PubMed/NCBI

6 

Ramesh G and Reeves WB: TNFR2-mediated apoptosis and necrosis in cisplatin-induced acute renal failure. Am J Physiol Renal Physiol. 285:610–618. 2003.

7 

Faubel S, Lewis EC, Reznikov L, Ljubanovic D, Hoke TS, Somerset H, Oh DJ, Lu L, Klein CL, Dinarello CA and Edelstein CL: Cisplatin-induced acute renal failure is associated with an increase in the cytokines interleukin (IL)-1β, IL-18, IL-6, and neutrophil infiltration in the kidney. J Pharmacol and Exp Ther. 322:8–15. 2007. View Article : Google Scholar

8 

Mukaida N: Pathophysiological roles of interleukin-8/CXCL8 in pulmonary diseases. Am J Physiol Lung Cell Mol Physiol. 284:L566–L577. 2003.PubMed/NCBI

9 

Wang Y, Wang W, Wang L, Wang X and Xia J: Regulatory mechanisms of interleukin-8 production induced by tumor necrosis factor-α in human hepatocellular carcinoma cells. J Cell Mol Med. 16:496–506. 2012. View Article : Google Scholar

10 

Zhao X, Li F, Town JR, Zhang X, Wang W and Gordon JR: Humanized forms of the CXCR1/CXCR2 antagonist, bovine CXCL8(3-74)K11R/G31P, effectively block ELR-CXC chemokine activity and airway endotoxemia pathology. Int Immunopharmacol. 7:1723–1731. 2007. View Article : Google Scholar : PubMed/NCBI

11 

Zhao X, Town JR, Li F, Zhang X, Cockcroft DW and Gordon JR: ELR-CXC chemokine receptor antagonism targets inflammatory responses at multiple levels. J Immunol. 182:3213–3222. 2009. View Article : Google Scholar : PubMed/NCBI

12 

Gordon JR, Li F, Zhang X, Wang W, Zhao X and Nayyar A: The combined CXCR1/CXCR2 antagonist CXCL8(3-74)K11R/G31P blocks neutrophil infiltration, pyrexia, and pulmonary vascular pathology in endotoxemic animals. J Leukoc Biol. 78:1265–1272. 2005. View Article : Google Scholar : PubMed/NCBI

13 

Zhao X, Town JR, Li F, Li W, Zhang X and Gordon JR: Blockade of neutrophil responses in aspiration pneumonia via ELR-CXC chemokine antagonism does not predispose to airway bacterial outgrowth. Pulm Pharmacol Ther. 23:22–28. 2010. View Article : Google Scholar

14 

Zhao X, Town JR, Yang A, Zhang X, Paur N, Sawicki G and Gordon JR: A novel ELR-CXC chemokine antagonist reduces intestinal ischemia reperfusion-induced mortality, and local and remote organ injury. J Surg Res. 162:264–273. 2010. View Article : Google Scholar

15 

Liu X, Peng J, Sun W, Yang S, Deng G, Li F, Cheng JW and Gordon JR: G31P, an antagonist against CXC chemokine receptors 1 and 2, inhibits growth of human prostate cancer cells in nude mice. Tohoku J Exp Med. 228:147–156. 2012. View Article : Google Scholar : PubMed/NCBI

16 

Qin Y, Fan F, Zhao Y, Cui Y, Wei X, Kohama K, Gordon JR, Li F and Gao Y: Recombinant human CXCL8 (3-72) K11R/G31P regulates smooth muscle cell proliferation and migration through blockage of interleukin-8 receptor. IUBMB Life. 65:67–75. 2013. View Article : Google Scholar : PubMed/NCBI

17 

Wei J, Peng J, Wang B, Qu H, Wang S, Faisal A, Cheng JW, Gordon JR and Li F: CXCR1/CXCR2 antagonism is effective in pulmonary defense against Klebsiella pneumoniae infection. Biomed Res Int. 2013:7209752013. View Article : Google Scholar : PubMed/NCBI

18 

Shen DW, Pouliot LM, Hall MD and Gottesman MM: Cisplatin resistance: a cellular self-defense mechanism resulting from multiple epigenetic and genetic changes. Pharmacol Rev. 64:706–721. 2012. View Article : Google Scholar : PubMed/NCBI

19 

Friedewald JJ and Rabb H: Inflammatory cells in ischemic acute renal failure. Kidney Int. 66:486–491. 2004. View Article : Google Scholar : PubMed/NCBI

20 

Okusa MD: The inflammatory cascade in acute ischemic renal failure. Nephron. 90:133–138. 2002. View Article : Google Scholar : PubMed/NCBI

21 

Wang W, Qin SK, Chen BA and Chen HY: Experimental study on antitumor effect of arsenic trioxide in combination with cisplatin or doxorubicin on hepatocellular carcinoma. World J Gastroenterol. 7:702–705. 2001.

22 

Yuan A, Chen JJ, Yao PL and Yang PC: The role of interleukin-8 in cancer cells and microenvironment interaction. Front Biosci. 10:853–865. 2005. View Article : Google Scholar

23 

Xie K: Interleukin-8 and human cancer biology. Cytokine Growth Factor Rev. 12:375–391. 2001. View Article : Google Scholar : PubMed/NCBI

24 

Harimoto N, Shirabe K, Abe T, et al: Interleukin-8 producing hepatocellular carcinoma with pyrexia. HPB Surg. 1:461–492. 2009.

25 

Yoong KF, Afford SC, Jones R, Aujla P, Qin S, Price K, Hubscher SG and Adams DH: Expression and function of CXC and CC chemokines in human malignant liver tumors: a role for human monokine induced by gamma-interferon in lymphocyte recruitment to hepatocellular carcinoma. Hepatology. 30:100–111. 1999. View Article : Google Scholar : PubMed/NCBI

26 

Yang ZF and Poon RT: Vascular changes in hepatocellular carcinoma. Anat Rec. 291:721–734. 2008. View Article : Google Scholar

27 

Tanaka H, Yamamoto M, Hashimoto N, Miyakoshi M, Tamakawa S, Yoshie M, Okusashi Y, Yokoyama K, Yaginuma Y and Ogawa K: Hypoxia-independent overexpression of hypoxia-inducible factor 1α as an early change in mouse hepatocarcinogenesis. Cancer Res. 66:11263–11270. 2006. View Article : Google Scholar : PubMed/NCBI

28 

Luppi F, Longo AM, de Boer WI, Rabe KF and Hiemstra PS: Interleukin-8 stimulates cell proliferation in non-small cell lung cancer through epidermal growth factor receptor transactivation. Lung Cancer. 56:25–33. 2007. View Article : Google Scholar

29 

Wu Y and Zhou BP: TNF-α/NF-κB/Snail pathway in cancer cell migration and invasion. Br J Cancer. 102:639–644. 2010. View Article : Google Scholar : PubMed/NCBI

30 

Guilpain P, Servettaz A, Batteux F, Guillevin L and Mouthon L: Natural and disease associated anti-myeloperoxidase (MPO) autoantibodies. Autoimmun Rev. 7:421–425. 2008. View Article : Google Scholar : PubMed/NCBI

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Copy and paste a formatted citation
Spandidos Publications style
Li L, Khan MN, Li Q, Chen X, Wei J, Wang B, Cheng J, Gordon JR and Li F: G31P, CXCR1/2 inhibitor, with cisplatin inhibits the growth of mice hepatocellular carcinoma and mitigates high‑dose cisplatin-induced nephrotoxicity. Oncol Rep 33: 751-757, 2015.
APA
Li, L., Khan, M.N., Li, Q., Chen, X., Wei, J., Wang, B. ... Li, F. (2015). G31P, CXCR1/2 inhibitor, with cisplatin inhibits the growth of mice hepatocellular carcinoma and mitigates high‑dose cisplatin-induced nephrotoxicity. Oncology Reports, 33, 751-757. https://doi.org/10.3892/or.2014.3659
MLA
Li, L., Khan, M. N., Li, Q., Chen, X., Wei, J., Wang, B., Cheng, J., Gordon, J. R., Li, F."G31P, CXCR1/2 inhibitor, with cisplatin inhibits the growth of mice hepatocellular carcinoma and mitigates high‑dose cisplatin-induced nephrotoxicity". Oncology Reports 33.2 (2015): 751-757.
Chicago
Li, L., Khan, M. N., Li, Q., Chen, X., Wei, J., Wang, B., Cheng, J., Gordon, J. R., Li, F."G31P, CXCR1/2 inhibitor, with cisplatin inhibits the growth of mice hepatocellular carcinoma and mitigates high‑dose cisplatin-induced nephrotoxicity". Oncology Reports 33, no. 2 (2015): 751-757. https://doi.org/10.3892/or.2014.3659
Copy and paste a formatted citation
x
Spandidos Publications style
Li L, Khan MN, Li Q, Chen X, Wei J, Wang B, Cheng J, Gordon JR and Li F: G31P, CXCR1/2 inhibitor, with cisplatin inhibits the growth of mice hepatocellular carcinoma and mitigates high‑dose cisplatin-induced nephrotoxicity. Oncol Rep 33: 751-757, 2015.
APA
Li, L., Khan, M.N., Li, Q., Chen, X., Wei, J., Wang, B. ... Li, F. (2015). G31P, CXCR1/2 inhibitor, with cisplatin inhibits the growth of mice hepatocellular carcinoma and mitigates high‑dose cisplatin-induced nephrotoxicity. Oncology Reports, 33, 751-757. https://doi.org/10.3892/or.2014.3659
MLA
Li, L., Khan, M. N., Li, Q., Chen, X., Wei, J., Wang, B., Cheng, J., Gordon, J. R., Li, F."G31P, CXCR1/2 inhibitor, with cisplatin inhibits the growth of mice hepatocellular carcinoma and mitigates high‑dose cisplatin-induced nephrotoxicity". Oncology Reports 33.2 (2015): 751-757.
Chicago
Li, L., Khan, M. N., Li, Q., Chen, X., Wei, J., Wang, B., Cheng, J., Gordon, J. R., Li, F."G31P, CXCR1/2 inhibitor, with cisplatin inhibits the growth of mice hepatocellular carcinoma and mitigates high‑dose cisplatin-induced nephrotoxicity". Oncology Reports 33, no. 2 (2015): 751-757. https://doi.org/10.3892/or.2014.3659
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