Open Access

Combining CXCL10 gene therapy and radiotherapy improved therapeutic efficacy in cervical cancer HeLa cell xenograft tumor models

  • Authors:
    • Ming Zhao
    • Qian Ma
    • Jinhui Xu
    • Shaozhi Fu
    • Lanlan Chen
    • Biqiong Wang
    • Jingbo Wu
    • Linglin Yang
  • View Affiliations

  • Published online on: May 27, 2015     https://doi.org/10.3892/ol.2015.3281
  • Pages: 768-772
  • Copyright: © Zhao et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Radiotherapy is an important treatment method for cervical cancer, but the efficacy requires improvement. Therefore, novel methods of treatment are required. Previous data have demonstrated that the CXC chemokine ligand 10 (CXCL10) inhibits angiogenesis, induces apoptosis and causes avoidance of the S phase of the cell cycle in cervical cancer cells. The aim of the present study was to evaluate the anti‑tumor effect of radiotherapy combined with CXCL10 gene therapy. Mouse models of cervical carcinoma were created by inoculation with HeLa cells, and were treated by combining intravenously administered plasmid‑encoding CXCL10, administered 5 times (days 12, 15, 18, 21 and 24 following inoculation), with direct radiation (20 Gy/5 fractions) administered on 5 consecutive days (~day 27 after inoculation). The vessel density and tumor cell proliferation were observed by immunostaining, and apoptosis was determined using a TUNEL assay. The results revealed a significant increase in the inhibition of tumor growth, reduced vessel density, decreased cell proliferation and increased apoptosis in the tumor cells of the combination therapy group. Overall, these findings resulted in the conclusion that CXCL10 gene therapy in combination with radiotherapy is a novel effective therapeutic strategy for cervical cancer.

References

1 

Schiffman M and Castle PE: The promise of global cervical cancer prevention. N Engl J Med. 353:2101–2104. 2005. View Article : Google Scholar : PubMed/NCBI

2 

Mandelblatt JS, Lawrence WF, Womack SM, Jacobson D, Yi B, Hwang YT, Gold K, Barter J and Shah K: Benefts and costs of using HPV testing to screen for cervical cancer. JAMA. 287:2372–2381. 2002. View Article : Google Scholar : PubMed/NCBI

3 

Small W Jr, Mell LK, Anderson P, et al: Consensus guidelines for delineation of clinical target volume for intensity-modulated pelvic radiotherapy in postoperative treatment of endometrial and cervical cancer. Int J Radiat Oncol Biol Phys. 71:428–434. 2008. View Article : Google Scholar : PubMed/NCBI

4 

Grigsby PW: Radiotherapy for pelvic recurrence after radical hysterectomy for cervical cancer. Radiat Med. 23:327–330. 2005.PubMed/NCBI

5 

Klopp AH and Eifel PJ: Chemoradiotherapy for cervical cancer in 2010. Curr Oncol Rep. 13:77–85. 2011. View Article : Google Scholar : PubMed/NCBI

6 

Tanderup K, Georg D, Pötter R, Kirisits C, Grau C and Lindegaard JC: Adaptive management of cervical cancer radiotherapy. Semin Radiat Oncol. 20:121–129. 2010. View Article : Google Scholar : PubMed/NCBI

7 

Bromley SK, Mempel TR and Luster AD: Orchestrating the orchestrators: Chemokines in control of T cell traffic. Nat Immunol. 9:970–980. 2008. View Article : Google Scholar : PubMed/NCBI

8 

Luster AD, Unkeless JC and Ravetch JV: Gamma-interferon transcriptionally regulates an early-response gene containing homology to platelet proteins. Nature. 315:672–676. 1985. View Article : Google Scholar : PubMed/NCBI

9 

Campanella GS, Colvin RA and Luster AD: CXCL10 can inhibit endothelial cell proliferation independently of CXCR3. PLoS One. 5:e127002010. View Article : Google Scholar : PubMed/NCBI

10 

Arenberg DA, Kunkel SL, Polverini PJ, Morris SB, et al: Interferon-gamma-inducible protein 10 (IP-10) is an angiostatic factor that inhibits human non-small cell lung cancer (NSCLC) tumorigenesis and spontaneous metastases. J Exp Med. 184:981–992. 1996. View Article : Google Scholar : PubMed/NCBI

11 

Pertl U, Luster AD, Varki NM, Homann D, Gaedicke G, Reisfeld RA and Lode HN: IFN-gamma-inducible protein-10 is essential for the generation of a protective tumor-specific CD8 T cell response induced by single-chain IL-12 gene therapy. J Immunol. 166:6944–6951. 2001. View Article : Google Scholar : PubMed/NCBI

12 

Feldman AL, Friedl J, Lans TE, et al: Retroviral gene transfer of interferon-inducible protein 10 inhibits growth of human melanoma xenografts. Int J Cancer. 99:149–159. 2002. View Article : Google Scholar : PubMed/NCBI

13 

Yang LL, Chen P, Luo S, Li J, Liu K, Hu HZ and Wei YQ: CXC-chemokine-ligand-10 gene therapy efficiently inhibits the growth of cervical carcinoma on the basis of its anti-angiogenic and antiviral activity. Biotechnol Appl Biochem. 53:209–216. 2009.PubMed/NCBI

14 

Yang LL, Wang BQ, Chen LL, Luo HQ and Wu JB: CXCL10 enhances radiotherapy effects in HeLa cells through cell cycle redistribution. Onclogy Lett. 3:383–386. 2012.

15 

Xiao F, Wei Y, Yang L, et al: A gene therapy for cancer based on the angiogenesis inhibitor, vasostatin. Gene Ther. 9:1207–1213. 2002. View Article : Google Scholar : PubMed/NCBI

16 

Somasundaram K and El-Deiry WS: Inhibition of p53-mediated transactivation and cell cycle arrest by E1A through its p300/CBP-interacting region. Oncogene. 14:1047–57. 1997. View Article : Google Scholar : PubMed/NCBI

17 

Li G, Tian L, Hou JM, et al: Improved therapeutic effectiveness by combining recombinant CXC chemokine ligand 10 with cisplatin in solid tumors. Clin Cancer Res. 11:4217–4224. 2005. View Article : Google Scholar : PubMed/NCBI

18 

Han GD, Suzuki K, Koike H, et al: IFN-inducible protein-10 plays a pivotal role in maintaining slit-diaphragm function by regulating podocyte cell-cycle balance. J Am Soc Nephrol. 17:442–453. 2006. View Article : Google Scholar : PubMed/NCBI

19 

Mazumder S, Plesca D and Almasan A: A jekyll and hyde role of cyclin E in the genotoxic stress response: switching from cell cycle control to apoptosis regulation. Cell Cycle. 6:1437–1442. 2007. View Article : Google Scholar : PubMed/NCBI

20 

Kawauchi S, Yamamoto Y, Uchida K, Chochi Y, Kondo T, Oga A and Sasaki K: Signifcance of cyclin E and p27 expression in malignant ovarian germ cell tumors: Correlation with the cell proliferation activity and clinicopathologic features. Oncol Rep. 16:1029–1033. 2006.PubMed/NCBI

21 

Frosina G: DNA repair and resistance of gliomas to chemotherapy and radiotherapy. Mol Cancer Res. 7:989–999. 2009. View Article : Google Scholar : PubMed/NCBI

22 

Pawlik TM and Keyomarsi K: Role of cell cycle in mediating sensitivity to radiotherapy. Int J Radiat Oncol Biol Phys. 59:928–942. 2004. View Article : Google Scholar : PubMed/NCBI

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August 2015
Volume 10 Issue 2

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Copy and paste a formatted citation
APA
Zhao, M., Ma, Q., Xu, J., Fu, S., Chen, L., Wang, B. ... Yang, L. (2015). Combining CXCL10 gene therapy and radiotherapy improved therapeutic efficacy in cervical cancer HeLa cell xenograft tumor models. Oncology Letters, 10, 768-772. https://doi.org/10.3892/ol.2015.3281
MLA
Zhao, M., Ma, Q., Xu, J., Fu, S., Chen, L., Wang, B., Wu, J., Yang, L."Combining CXCL10 gene therapy and radiotherapy improved therapeutic efficacy in cervical cancer HeLa cell xenograft tumor models". Oncology Letters 10.2 (2015): 768-772.
Chicago
Zhao, M., Ma, Q., Xu, J., Fu, S., Chen, L., Wang, B., Wu, J., Yang, L."Combining CXCL10 gene therapy and radiotherapy improved therapeutic efficacy in cervical cancer HeLa cell xenograft tumor models". Oncology Letters 10, no. 2 (2015): 768-772. https://doi.org/10.3892/ol.2015.3281