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Article

TCN, an AKT inhibitor, exhibits potent antitumor activity and enhances radiosensitivity in hypoxic esophageal squamous cell carcinoma in vitro and in vivo

  • Authors:
    • Qing Guo
    • Jia He
    • Feng Shen
    • Wei Zhang
    • Xi Yang
    • Chi Zhang
    • Qu Zhang
    • Jun‑Xing Huang
    • Zheng‑Dong Wu
    • Xin‑Chen Sun
    • Sheng‑Bin Dai
  • View Affiliations / Copyright

    Affiliations: Department of Radiotherapy, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210029, P.R. China, Department of Radiotherapy, People's Hospital of Jiangyin, Wuxi, Jiangsu 214400, P.R. China, Department of Oncology, People's Hospital of Taizhou, Taizhou, Jiangsu 225300, P.R. China, Department of Radiotherapy, Hubei Cancer Hospital, Wuhan, Hubei 430079, P.R. China
  • Pages: 949-954
    |
    Published online on: December 20, 2016
       https://doi.org/10.3892/ol.2016.5515
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Abstract

The aim of the present study was to investigate the radiosensitization effect of triciribine (TCN) on human esophageal squamous cell carcinoma (ESCC) in normoxia or hypoxia and its mechanism. The cytotoxicity and radiosensitization mechanism of TCN were investigated by Cell Counting Kit 8, clonogenic assay, flow cytometry, western blotting (WB) and immunofluorescence staining of phospho-histone H2A.X, Ser139 (γ‑H2AX) in ESCC in vitro, while the protein expression levels of AKT, phosphorylated (p)‑AKT, hypoxia-inducible factor (HIF)‑1α and vascular endothelial growth factor (VEGF) were evaluated by WB in vivo. The cytotoxicity of TCN was dose dependent. Upon exposure to TCN, ESCC cells in hypoxia treated with 4‑Gy radiotherapy exhibited an evidently higher apoptotic rate than cells subjected to other treatments. TCN could significantly inhibit the protein expression of p‑AKT, HIF‑1α and VEGF in vitro and in vivo. The present results suggested that TCN can effectively inhibit AKT, p‑AKT, HIF‑1α and VEGF, thus conferring radiosensitivity to ESCC in vitro and vivo. TCN is considered as an adjuvant in radiotherapy of ESCC in clinical application.
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View References

1 

National Cancer Institute, . Cancer Statistics: SEER Stat Fact Sheets: Esophageal Cancer. http://seer.cancer.gov/statfacts/html/esoph.htmlAccessed January 1, 2014.

2 

Gholipour C, Shalchi RA and Abbasi M: A histopathological study of esophageal cancer on the western side of the Caspian littoral from 1994 to 2003. Dis Esophagus. 21:322–327. 2008. View Article : Google Scholar : PubMed/NCBI

3 

Tran GD, Sun XD, Abnet CC, Fan JH, Dawsey SM, Dong ZW, Mark SD, Qiao YL and Taylor PR: Prospective study of risk factors for esophageal and gastric cancers in the Linxian general population trial cohort in China. Int J Cancer. 113:456–463. 2005. View Article : Google Scholar : PubMed/NCBI

4 

Tepper J, Krasna MJ, Niedzwiecki D, Hollis D, Reed CE, Goldberg R, Kiel K, Willett C, Sugarbaker D and Mayer R: Phase III trial of trimodality therapy with cisplatin, fluorouracil, radiotherapy, and surgery compared with surgery alone for esophageal cancer: CALGB 9781. J Clin Oncol. 26:1086–1092. 2008. View Article : Google Scholar : PubMed/NCBI

5 

Liu HC, Hung SK, Huang CJ, Chen CC, Chen MJ, Chang CC, Tai CJ, Tzen CY, Lu LH and Chen YJ: Esophagectomy for locally advanced esophageal cancer, followed by chemoradiotherapy and adjuvant chemotherapy. World J Gastroenterol. 11:5367–5372. 2005. View Article : Google Scholar : PubMed/NCBI

6 

Karar J and Maity A: Modulating the tumor microenvironment to increase radiation responsiveness. Cancer Biol Ther. 8:1994–2001. 2009. View Article : Google Scholar : PubMed/NCBI

7 

Davies MA: Regulation, role, and targeting of Akt in cancer. J Clin Oncol. 29:4715–4717. 2011. View Article : Google Scholar : PubMed/NCBI

8 

Courtney KD, Corcoran RB and Engelman JA: The PI3K pathway as drug target in human cancer. J Clin Oncol. 28:1075–1083. 2010. View Article : Google Scholar : PubMed/NCBI

9 

Hasselblom S, Hansson U, Olsson M, Torén L, Bergström A, Nilsson-Ehle H and Andersson PO: High immunohistochemical expression of p-AKT predicts inferior survival in patients with diffuse large B-cell lymphoma treated with immunochemotherapy. Br J Haematol. 149:560–568. 2010. View Article : Google Scholar : PubMed/NCBI

10 

Hong JY, Hong ME, Choi MK, Kim YS, Chang W, Maeng CH, Park S, Lee SJ, Do IG, Jo JS, et al: The impact of activated p-AKT expression on clinical outcomes in diffuse large B-cell lymphoma: A clinicopathological study of 262 cases. Ann Oncol. 25:182–188. 2014. View Article : Google Scholar : PubMed/NCBI

11 

Cummins EP and Taylor CT: Hypoxia-responsive transcription factors. Pflugers Arch. 450:363–371. 2005. View Article : Google Scholar : PubMed/NCBI

12 

Jung JE, Lee HG, Cho IH, Chung DH, Yoon SH, Yang YM, Lee JW, Choi S, Park JW, Ye SK and Chung MH: STAT3 is a potential modulator of HIF-1-mediated VEGF expression in human renal carcinoma cells. FASEB J. 19:1296–1298. 2005.PubMed/NCBI

13 

Xu Q, Briggs J, Park S, Niu G, Kortylewski M, Zhang S, Gritsko T, Turkson J, Kay H, Semenza GL, et al: Targeting Stat3 blocks both HIF-1 and VEGF expression induced by multiple oncogenic growth signaling pathways. Oncogene. 24:5552–5560. 2005. View Article : Google Scholar : PubMed/NCBI

14 

Liao D and Johnson RS: Hypoxia: A key regulator of angiogenesis in cancer. Cancer Metastasis Rev. 26:281–290. 2007. View Article : Google Scholar : PubMed/NCBI

15 

Yang X, Zhu HC, Zhang C, Qin Q, Liu J, Xu LP, Zhao LJ, Zhang Q, Cai J, Ma JX, et al: HIF-1α; 1772 C/T and 1790 G/A polymorphisms are significantly associated with higher cancer risk: An updated meta-analysis from 34 case-control studies. PLoS One. 8:e803962013. View Article : Google Scholar : PubMed/NCBI

16 

Yang X, Zhang C, Zhu HC, Qin Q, Zhao LJ, Liu J, Xu LP, Zhang Q, Cai J, Ma JX, et al: HIF-1α P582S and A588T polymorphisms and digestive system cancer risk-a meta-analysis. Tumour Biol. 35:2825–2830. 2014. View Article : Google Scholar : PubMed/NCBI

17 

Guo Q, Dai SB, Shen F, Yu D, Shen ST, Zhang Q, Huang JX and Wu ZD: VEGF+405G/C (rs2010963) polymorphisms and digestive system cancer risk: A meta-analysis. Tumour Biol. 35:4977–4982. 2014. View Article : Google Scholar : PubMed/NCBI

18 

Gürsel DB, ConnellAlbert YS, Tuskan RG, Anastassiadis T, Walrath JC, Hawes JJ, Amlin-Van Schaick JC and Reilly KM: Control of proliferation in astrocytoma cells by the receptor tyrosine kinase/PI3K/AKT signaling axis and the use of PI-103 and TCN as potential anti-astrocytoma therapies. Neuro Oncol. 13:610–621. 2011. View Article : Google Scholar : PubMed/NCBI

19 

Dieterle A, Orth R, Daubrawa M, Grotemeier A, Alers S, Ullrich S, Lammers R, Wesselborg S and Stork B: The Akt inhibitor triciribine sensitizes prostate carcinoma cells to TRAIL-induced apoptosis. Int J Cancer. 125:932–941. 2009. View Article : Google Scholar : PubMed/NCBI

20 

Kesari S, Advani SJ, Lawson JD, Kahle KT, Ng K, Carter B and Chen CC: DNA damage response and repair: Insights into strategies for radiation sensitization of gliomas. Future Oncol. 7:1335–1346. 2011. View Article : Google Scholar : PubMed/NCBI

21 

Pajonk F, Vlashi E and McBride WH: Radiation resistance of cancer stem cells: The 4 R's of radiobiology revisited. Stem Cells. 28:639–648. 2010. View Article : Google Scholar : PubMed/NCBI

22 

Ahmed KM and Li JJ: NF-κB-mediated adaptive resistance to ionizing radiation. Free Radic Biol Med. 44:1–13. 2008. View Article : Google Scholar : PubMed/NCBI

23 

Zhang C, Yang X, Zhang Q, Guo Q, He J, Qin Q, Zhu H, Liu J, Zhan L, Lu J, et al: STAT3 inhibitor NSC74859 radiosensitizes esophageal cancer via the downregulation of HIF-1α. Tumour Biol. 35:9793–9799. 2014. View Article : Google Scholar : PubMed/NCBI

24 

Zhang Q, Zhang C, He J, Guo Q, Hu D, Yang X, Wang J, Kang Y, She R, Wang Z, et al: STAT3 inhibitor stattic enhances radiosensitivity in esophageal squamous cell carcinoma. Tumour Biol. 36:2135–2142. 2015. View Article : Google Scholar : PubMed/NCBI

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Copy and paste a formatted citation
Spandidos Publications style
Guo Q, He J, Shen F, Zhang W, Yang X, Zhang C, Zhang Q, Huang JX, Wu ZD, Sun XC, Sun XC, et al: TCN, an AKT inhibitor, exhibits potent antitumor activity and enhances radiosensitivity in hypoxic esophageal squamous cell carcinoma in vitro and in vivo. Oncol Lett 13: 949-954, 2017.
APA
Guo, Q., He, J., Shen, F., Zhang, W., Yang, X., Zhang, C. ... Dai, S. (2017). TCN, an AKT inhibitor, exhibits potent antitumor activity and enhances radiosensitivity in hypoxic esophageal squamous cell carcinoma in vitro and in vivo. Oncology Letters, 13, 949-954. https://doi.org/10.3892/ol.2016.5515
MLA
Guo, Q., He, J., Shen, F., Zhang, W., Yang, X., Zhang, C., Zhang, Q., Huang, J., Wu, Z., Sun, X., Dai, S."TCN, an AKT inhibitor, exhibits potent antitumor activity and enhances radiosensitivity in hypoxic esophageal squamous cell carcinoma in vitro and in vivo". Oncology Letters 13.2 (2017): 949-954.
Chicago
Guo, Q., He, J., Shen, F., Zhang, W., Yang, X., Zhang, C., Zhang, Q., Huang, J., Wu, Z., Sun, X., Dai, S."TCN, an AKT inhibitor, exhibits potent antitumor activity and enhances radiosensitivity in hypoxic esophageal squamous cell carcinoma in vitro and in vivo". Oncology Letters 13, no. 2 (2017): 949-954. https://doi.org/10.3892/ol.2016.5515
Copy and paste a formatted citation
x
Spandidos Publications style
Guo Q, He J, Shen F, Zhang W, Yang X, Zhang C, Zhang Q, Huang JX, Wu ZD, Sun XC, Sun XC, et al: TCN, an AKT inhibitor, exhibits potent antitumor activity and enhances radiosensitivity in hypoxic esophageal squamous cell carcinoma in vitro and in vivo. Oncol Lett 13: 949-954, 2017.
APA
Guo, Q., He, J., Shen, F., Zhang, W., Yang, X., Zhang, C. ... Dai, S. (2017). TCN, an AKT inhibitor, exhibits potent antitumor activity and enhances radiosensitivity in hypoxic esophageal squamous cell carcinoma in vitro and in vivo. Oncology Letters, 13, 949-954. https://doi.org/10.3892/ol.2016.5515
MLA
Guo, Q., He, J., Shen, F., Zhang, W., Yang, X., Zhang, C., Zhang, Q., Huang, J., Wu, Z., Sun, X., Dai, S."TCN, an AKT inhibitor, exhibits potent antitumor activity and enhances radiosensitivity in hypoxic esophageal squamous cell carcinoma in vitro and in vivo". Oncology Letters 13.2 (2017): 949-954.
Chicago
Guo, Q., He, J., Shen, F., Zhang, W., Yang, X., Zhang, C., Zhang, Q., Huang, J., Wu, Z., Sun, X., Dai, S."TCN, an AKT inhibitor, exhibits potent antitumor activity and enhances radiosensitivity in hypoxic esophageal squamous cell carcinoma in vitro and in vivo". Oncology Letters 13, no. 2 (2017): 949-954. https://doi.org/10.3892/ol.2016.5515
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