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Article

Herpes simplex virus type 1 VP22-mediated intercellular delivery of PTEN increases the antitumor activity of PTEN in esophageal squamous cell carcinoma cells in vitro and in vivo

  • Authors:
    • Xian Yu
    • Tingting Li
    • Yifan Xia
    • Jun Lei
    • Yan Wang
    • Lijuan Zhang
  • View Affiliations / Copyright

    Affiliations: Department of Pharmacy, The Second Affiliated Hospital, Chongqing Medical University, Chongqing 400010, P.R. China, Institute of Materia Medica, North Sichuan Medical College, Nanchong, Sichuan 637007, P.R. China, Department of Orthopaedics, Chongqing General Hospital, Chongqing 400014, P.R. China
  • Pages: 3034-3040
    |
    Published online on: March 18, 2016
       https://doi.org/10.3892/or.2016.4694
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Abstract

In the past decade, studies have revealed that the phosphatase and tensin homolog (PTEN) protein, a tumor suppressor, comprises a potential biological marker and therapeutic target for esophageal squamous cell carcinoma (ESCC). As such, the delivery of the PTEN gene represents a powerful strategy for ESCC therapy. The tegument protein VP22 of herpes simplex virus type 1 (HSV-1) has been reported to act as a transporter of heterologous proteins across the host cell membrane, thereby enhancing the biological functions of these proteins. In the present study, the intercellular delivery and antitumor activity of the fusion protein PTEN-VP22 were examined in the esophageal squamous cell carcinoma cell line Eca109 both in vitro and in vivo. VP22-mediated PTEN intercellular delivery was confirmed in the Eca109 cells by western blot analysis and by quantitation of immunofluorescence. VP22 alone did not exert antiproliferative effects or induce cell cycle arrest, induction of apoptosis, blockage of the Akt and focal adhesion kinase (FAK) pathways, tumor growth inhibition, or antiangiogenic effects in Eca109 cells. However, compared with PTEN alone, PTEN-VP22 exerted significantly higher antiproliferative effects and induced cell cycle arrest at G1 stage, apoptosis and antiangiogenic effects in Eca109 cells. Together, our findings demonstrate that VP22 alone does not exert antitumor activity directly; however, this protein mediates the intercellular delivery of PTEN and thereby increases its intracellular concentration to achieve a therapeutic steady state, leading to an overall increase in the antitumor activity of PTEN. This study provides further experimental data to confirm the potential of VP22-based intercellular delivery strategies for enhancing the efficacy of gene therapy for cancer treatment.
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1 

Enzinger PC and Mayer RJ: Esophageal cancer. N Engl J Med. 349:2241–2252. 2003. View Article : Google Scholar : PubMed/NCBI

2 

Pennathur A, Gibson MK, Jobe BA and Luketich JD: Oesophageal carcinoma. Lancet. 381:400–412. 2013. View Article : Google Scholar : PubMed/NCBI

3 

Kamangar F, Dores GM and Anderson WF: Patterns of cancer incidence, mortality, and prevalence across five continents: Defining priorities to reduce cancer disparities in different geographic regions of the world. J Clin Oncol. 24:2137–2150. 2006. View Article : Google Scholar : PubMed/NCBI

4 

Terakawa N, Kanamori Y and Yoshida S: Loss of PTEN expression followed by Akt phosphorylation is a poor prognostic factor for patients with endometrial cancer. Endocr Relat Cancer. 10:203–208. 2003. View Article : Google Scholar : PubMed/NCBI

5 

Kondo Y, Hollingsworth EF and Kondo S: Molecular targeting for malignant gliomas (Review). Int J Oncol. 24:1101–1109. 2004.PubMed/NCBI

6 

Koksal IT, Dirice E, Yasar D, Sanlioglu AD, Ciftcioglu A, Gulkesen KH, Ozes NO, Baykara M, Luleci G and Sanlioglu S: The assessment of PTEN tumor suppressor gene in combination with Gleason scoring and serum PSA to evaluate progression of prostate carcinoma. Urol Oncol. 22:307–312. 2004. View Article : Google Scholar : PubMed/NCBI

7 

Im SA, Lee KE, Nam E, Kim DY, Lee JH, Han HS, Seoh JY, Park HY, Cho MS, Han WS, et al: Potential prognostic significance of p185(HER2) overexpression with loss of PTEN expression in gastric carcinomas. Tumori. 91:513–521. 2005.

8 

Tang JM, He QY, Guo RX and Chang XJ: Phosphorylated Akt overexpression and loss of PTEN expression in non-small cell lung cancer confers poor prognosis. Lung Cancer. 51:181–191. 2006. View Article : Google Scholar

9 

Toft DJ and Cryns VL: Minireview: Basal-like breast cancer: from molecular profiles to targeted therapies. Mol Endocrinol. 25:199–211. 2011. View Article : Google Scholar :

10 

Tachibana M, Shibakita M, Ohno S, Kinugasa S, Yoshimura H, Ueda S, Fujii T, Rahman MA, Dhar DK and Nagasue N: Expression and prognostic significance of PTEN product protein in patients with esophageal squamous cell carcinoma. Cancer. 94:1955–1960. 2002. View Article : Google Scholar : PubMed/NCBI

11 

Li P, Mao WM, Zheng ZG, Dong ZM and Ling ZQ: Down-regulation of PTEN expression modulated by dysregulated miR-21 contributes to the progression of esophageal cancer. Dig Dis Sci. 58:3483–3493. 2013. View Article : Google Scholar : PubMed/NCBI

12 

Sun Z, Ji N, Bi M, Zhang Z, Liu X and Wang Z: Negative expression of PTEN identifies high risk for lymphatic-related metastasis in human esophageal squamous cell carcinoma. Oncol Rep. 33:3024–3032. 2015.PubMed/NCBI

13 

Zhao H, Yang J, Fan T, Li S and Ren X: RhoE functions as a tumor suppressor in esophageal squamous cell carcinoma and modulates the PTEN/PI3K/Akt signaling pathway. Tumour Biol. 33:1363–1374. 2012. View Article : Google Scholar : PubMed/NCBI

14 

Ou Y, Ma L, Ma L, Huang Z, Zhou W, Zhao C, Zhang B, Song Y, Yu C and Zhan Q: Overexpression of cyclin B1 antagonizes chemotherapeutic-induced apoptosis through PTEN/Akt pathway in human esophageal squamous cell carcinoma cells. Cancer Biol Ther. 14:45–55. 2013. View Article : Google Scholar :

15 

Sun MM, Zhang MZ, Chen Y, Li SL, Zhang W, Ya GW and Chen KS: Effect of PTEN antisense oligonucleotide on oesophageal squamous cell carcinoma cell lines. J Int Med Res. 40:2098–2108. 2012. View Article : Google Scholar

16 

Zhou YA, Zhang T, Zhao JB, Wang XP, Jiang T, Gu ZP, Wang XN and Li XF: The adenovirus-mediated transfer of PTEN inhibits the growth of esophageal cancer cells in vitro and in vivo. Biosci Biotechnol Biochem. 74:736–740. 2010. View Article : Google Scholar : PubMed/NCBI

17 

Wills KN, Atencio IA, Avanzini JB, Neuteboom S, Phelan A, Philopena J, Sutjipto S, Vaillancourt MT, Wen SF, Ralston RO, et al: Intratumoral spread and increased efficacy of a p53-VP22 fusion protein expressed by a recombinant adenovirus. J Virol. 75:8733–8741. 2001. View Article : Google Scholar : PubMed/NCBI

18 

Zavaglia D, Favrot MC, Eymin B, Tenaud C and Coll JL: Intercellular trafficking and enhanced in vivo antitumour activity of a non-virally delivered P27-VP22 fusion protein. Gene Ther. 10:314–325. 2003. View Article : Google Scholar : PubMed/NCBI

19 

Jin G, Zhou Y, Chai Q, Zhu G, Xu F and Liu F: VP22 and cytosine deaminase fusion gene modified tissue-engineered neural stem cells for glioma therapy. J Cancer Res Clin Oncol. 139:475–483. 2013. View Article : Google Scholar

20 

Nishikawa M, Otsuki T, Ota A, Guan X, Takemoto S, Takahashi Y and Takakura Y: Induction of tumor-specific immune response by gene transfer of Hsp70-cell-penetrating peptide fusion protein to tumors in mice. Mol Ther. 18:421–428. 2010. View Article : Google Scholar :

21 

Yu X, Xu Z, Lei J, Li T and Wang Y: VP22 mediates intercellular trafficking and enhances the in vitro antitumor activity of PTEN. Mol Med Rep. 12:1286–1290. 2015.PubMed/NCBI

22 

Regberg J, Srimanee A and Langel U: Applications of cell-penetrating peptides for tumor targeting and future cancer therapies. Pharmaceuticals (Basel). 5:991–1007. 2012. View Article : Google Scholar

23 

Kueltzo LA, Normand N, O'Hare P and Middaugh CR: Conformational lability of herpesvirus protein VP22. J Biol Chem. 275:33213–33221. 2000. View Article : Google Scholar : PubMed/NCBI

24 

Elliott G and O'Hare P: Intercellular trafficking and protein delivery by a herpesvirus structural protein. Cell. 88:223–233. 1997. View Article : Google Scholar : PubMed/NCBI

25 

Persad S, Attwell S, Gray V, Delcommenne M, Troussard A, Sanghera J and Dedhar S: Inhibition of integrin-linked kinase (ILK) suppresses activation of protein kinase B/Akt and induces cell cycle arrest and apoptosis of PTEN-mutant prostate cancer cells. Proc Natl Acad Sci USA. 97:3207–3212. 2000. View Article : Google Scholar : PubMed/NCBI

26 

Li Z, Liu GX, Liu YL, Chen X, Huang XL and Gan HT: Effect of adenovirus-mediated PTEN gene on ulcerative colitis-associated colorectal cancer. Int J Colorectal Dis. 28:1107–1115. 2013. View Article : Google Scholar : PubMed/NCBI

27 

Maehama T and Dixon JE: The tumor suppressor, PTEN/MMAC1, dephosphorylates the lipid second messenger, phosphatidylinositol 3,4,5-trisphosphate. J Biol Chem. 273:13375–13378. 1998. View Article : Google Scholar : PubMed/NCBI

28 

Cully M, You H, Levine AJ and Mak TW: Beyond PTEN mutations: The PI3K pathway as an integrator of multiple inputs during tumorigenesis. Nat Rev Cancer. 6:184–192. 2006. View Article : Google Scholar : PubMed/NCBI

29 

Leslie NR, Yang X, Downes CP and Weijer CJ: PtdIns(3,4,5) P(3)-dependent and -independent roles for PTEN in the control of cell migration. Curr Biol. 17:115–125. 2007. View Article : Google Scholar : PubMed/NCBI

30 

Schwock J, Dhani N and Hedley DW: Targeting focal adhesion kinase signaling in tumor growth and metastasis. Expert Opin Ther Targets. 14:77–94. 2010. View Article : Google Scholar

31 

Sieg DJ, Hauck CR, Ilic D, Klingbeil CK, Schaefer E, Damsky CH and Schlaepfer DD: FAK integrates growth-factor and integrin signals to promote cell migration. Nat Cell Biol. 2:249–256. 2000. View Article : Google Scholar : PubMed/NCBI

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Copy and paste a formatted citation
Spandidos Publications style
Yu X, Li T, Xia Y, Lei J, Wang Y and Zhang L: Herpes simplex virus type 1 VP22-mediated intercellular delivery of PTEN increases the antitumor activity of PTEN in esophageal squamous cell carcinoma cells in vitro and in vivo. Oncol Rep 35: 3034-3040, 2016.
APA
Yu, X., Li, T., Xia, Y., Lei, J., Wang, Y., & Zhang, L. (2016). Herpes simplex virus type 1 VP22-mediated intercellular delivery of PTEN increases the antitumor activity of PTEN in esophageal squamous cell carcinoma cells in vitro and in vivo. Oncology Reports, 35, 3034-3040. https://doi.org/10.3892/or.2016.4694
MLA
Yu, X., Li, T., Xia, Y., Lei, J., Wang, Y., Zhang, L."Herpes simplex virus type 1 VP22-mediated intercellular delivery of PTEN increases the antitumor activity of PTEN in esophageal squamous cell carcinoma cells in vitro and in vivo". Oncology Reports 35.5 (2016): 3034-3040.
Chicago
Yu, X., Li, T., Xia, Y., Lei, J., Wang, Y., Zhang, L."Herpes simplex virus type 1 VP22-mediated intercellular delivery of PTEN increases the antitumor activity of PTEN in esophageal squamous cell carcinoma cells in vitro and in vivo". Oncology Reports 35, no. 5 (2016): 3034-3040. https://doi.org/10.3892/or.2016.4694
Copy and paste a formatted citation
x
Spandidos Publications style
Yu X, Li T, Xia Y, Lei J, Wang Y and Zhang L: Herpes simplex virus type 1 VP22-mediated intercellular delivery of PTEN increases the antitumor activity of PTEN in esophageal squamous cell carcinoma cells in vitro and in vivo. Oncol Rep 35: 3034-3040, 2016.
APA
Yu, X., Li, T., Xia, Y., Lei, J., Wang, Y., & Zhang, L. (2016). Herpes simplex virus type 1 VP22-mediated intercellular delivery of PTEN increases the antitumor activity of PTEN in esophageal squamous cell carcinoma cells in vitro and in vivo. Oncology Reports, 35, 3034-3040. https://doi.org/10.3892/or.2016.4694
MLA
Yu, X., Li, T., Xia, Y., Lei, J., Wang, Y., Zhang, L."Herpes simplex virus type 1 VP22-mediated intercellular delivery of PTEN increases the antitumor activity of PTEN in esophageal squamous cell carcinoma cells in vitro and in vivo". Oncology Reports 35.5 (2016): 3034-3040.
Chicago
Yu, X., Li, T., Xia, Y., Lei, J., Wang, Y., Zhang, L."Herpes simplex virus type 1 VP22-mediated intercellular delivery of PTEN increases the antitumor activity of PTEN in esophageal squamous cell carcinoma cells in vitro and in vivo". Oncology Reports 35, no. 5 (2016): 3034-3040. https://doi.org/10.3892/or.2016.4694
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