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Lentiviral vector with a radiation‑inducible promoter, carrying the ING4 gene, mediates radiosensitization controlled by radiotherapy in cervical cancer cells

  • Authors:
    • Tao Ma
    • Rui Guo
    • Xi Wang
    • Wen-Tong Shen
    • Min Zhu
    • Ye-Ning Jin
    • Hao-Ping Xu
  • View Affiliations / Copyright

    Affiliations: Department of Radiation Oncology, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200025, P.R. China, Department of Nuclear Medicine, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200025, P.R. China, Department of Neurology, Hackensack Meridian Health JFK Medical Center, Edison, NJ 08820, USA
    Copyright: © Ma et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 67
    |
    Published online on: November 25, 2020
       https://doi.org/10.3892/ol.2020.12328
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Abstract

The presence of hypoxia in solid tumors is considered one of the major factors that contribute to radiation resistance. The aim of the present study was to establish a therapeutic system, which can be controlled by radiation itself, to enhance radiosensitivity. For this purpose, a lentiviral gene therapy vector containing the human inhibitor of growth 4 (ING4) and its upstream promoter, human early growth response factor‑1 (EGR1), which possesses the radiation‑inducible characteristics to activate the transcription of its downstream genes, was constructed. Downstream fluorescence proteins were investigated to ensure that the EGR1 promoter was induced by irradiation. Furthermore, ING4 open reading frame (ORF) expression was detected by western blotting. The cell cycle was analyzed by fluorescence‑activated cell sorting analysis 48 h after the cells were exposed to X‑rays ranging between 0 and 8 Gy. In cells stably and transiently transfected with reporter plasmids, the EGR1‑driver gene was sensitive to ionizing irradiation. Furthermore, irradiation‑induced ING4 gene expression was observed. The enhanced ING4 expression increased the number of cells in the G2/M phase and decreased the proportion of cells in the G1/S phase. Therefore, ING4 expression inhibited cell proliferation and was associated with less colonies being formed. Furthermore, ING4 suppressed hypoxia‑inducible factor 1α expression under hypoxic conditions and promoted cell apoptosis. Overall, these results revealed that combining the EGR1 promoter and ING4 ORF using a lentivirus system may be a promising therapeutic strategy with which to enhance radiosensitivity controlled by radiation. However, further studies using in vivo models are required to confirm these findings.
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View References

1 

Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA and Jemal A: Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 68:394–424. 2018. View Article : Google Scholar : PubMed/NCBI

2 

Bhatla N, Berek JS, Fredes MC, Denny LA, Grenman S, Karunaratne K, Kehoe ST, Konishi I, Olawaiye AB, Prat J, et al: Revised FIGO staging for carcinoma of the cervix uteri. Int J Gynaecol Obstet. 145:129–135. 2019. View Article : Google Scholar : PubMed/NCBI

3 

Chino J, Annunziata CM, Beriwal S, Bradfield L, Erickson BA, Fields EC, Fitch K, Harkenrider MM, Holschneider CH, Kamrava M, et al: Radiation therapy for cervical cancer: Executive summary of an ASTRO clinical practice guideline. Pract Radiat Oncol. 10:220–234. 2020. View Article : Google Scholar : PubMed/NCBI

4 

Lukas J, Lukas C and Bartek J: Mammalian cell cycle checkpoints: Signalling pathways and their organization in space and time. DNA Repair (Amst). 3:997–1007. 2004. View Article : Google Scholar : PubMed/NCBI

5 

Zhao Y, Li Z, Sheng W, Miao J and Yang J: Radiosensitivity by ING4-IL-24 bicistronic adenovirus-mediated gene cotransfer on human breast cancer cells. Cancer Gene Ther. 20:38–45. 2013. View Article : Google Scholar : PubMed/NCBI

6 

Jiang X, Zhang QL, Tian YH, Huang JC and Ma GL: RNA interference-mediated gene silencing of cyclophilin A enhances the radiosensitivity of PAa human lung adenocarcinoma cells in vitro. Oncol Lett. 13:1619–1624. 2017. View Article : Google Scholar : PubMed/NCBI

7 

Liu Y, Yu L, Wang Y, Zhang Y, Wang Y and Zhang G: Expression of tumor suppressor gene ING4 in ovarian carcinoma is correlated with microvessel density. J Cancer Res Clin Oncol. 138:647–655. 2012. View Article : Google Scholar : PubMed/NCBI

8 

Gunduz M, Nagatsuka H, Demircan K, Gunduz E, Cengiz B, Ouchida M, Tsujigiwa H, Yamachika E, Fukushima K, Beder L, et al: Frequent deletion and down-regulation of ING4, a candidate tumor suppressor gene at 12p13, in head and neck squamous cell carcinomas. Gene. 356:109–117. 2005. View Article : Google Scholar : PubMed/NCBI

9 

Coles AH and Jones SN: The ING gene family in the regulation of cell growth and tumorigenesis. J Cell Physiol. 218:45–57. 2009. View Article : Google Scholar : PubMed/NCBI

10 

Xu M, Xie Y, Sheng W, Miao J and Yang J: Adenovirus-mediated ING4 gene transfer in osteosarcoma suppresses tumor growth via induction of apoptosis and inhibition of tumor angiogenesis. Technol Cancer Res Treat. 14:369–378. 2015. View Article : Google Scholar : PubMed/NCBI

11 

Yan R, He L, Li Z, Han X, Liang J, Si W, Chen Z, Li L, Xie G, Li W, et al: SCF(JFK) is a bona fide E3 ligase for ING4 and a potent promoter of the angiogenesis and metastasis of breast cancer. Genes Dev. 29:672–685. 2015. View Article : Google Scholar : PubMed/NCBI

12 

Weichselbaum RR and Kufe D: Translation of the radio- and chemo-inducible TNFerade vector to the treatment of human cancers. Cancer Gene Ther. 16:609–619. 2009. View Article : Google Scholar : PubMed/NCBI

13 

Kufe D and Weichselbaum R: Radiation therapy: Activation for gene transcription and the development of genetic radiotherapy-therapeutic strategies in oncology. Cancer Biol Ther. 2:326–329. 2003. View Article : Google Scholar : PubMed/NCBI

14 

Liu LL, Smith MJ, Sun BS, Wang GJ, Redmond HP and Wang JH: Combined IFN-gamma-endostatin gene therapy and radiotherapy attenuates primary breast tumor growth and lung metastases via enhanced CTL and NK cell activation and attenuated tumor angiogenesis in a murine model. Ann Surg Oncol. 16:1403–1411. 2009. View Article : Google Scholar : PubMed/NCBI

15 

Yang W and Li XY: Anti-tumor effect of pEgr-interferon-gamma-endostatin gene-radiotherapy in mice bearing Lewis lung carcinoma and its mechanism. Chin Med J (Engl). 118:296–301. 2005.PubMed/NCBI

16 

Arai M, Kawachi T, Setiawan A and Kobayashi M: Hypoxia-selective growth inhibition of cancer cells by furospinosulin-1, a furanosesterterpene isolated from an Indonesian marine sponge. ChemMedChem. 5:1919–26. 2010. View Article : Google Scholar : PubMed/NCBI

17 

Toma-Daşu I, Daşu A and Karlsson M: The relationship between temporal variation of hypoxia, polarographic measurements and predictions of tumour response to radiation. Phys Med Biol. 49:4463–4475. 2004. View Article : Google Scholar : PubMed/NCBI

18 

Hickey MM and Simon MC: Regulation of angiogenesis by hypoxia and hypoxia-inducible factors. Curr Top Dev Biol. 76:217–257. 2006. View Article : Google Scholar : PubMed/NCBI

19 

Leskov KS, Criswell T, Antonio S, Li J, Yang CR, Kinsella TJ and Boothman DA: When X-ray-inducible proteins meet DNA double strand break repair. Semin Radiat Oncol. 11:352–372. 2001. View Article : Google Scholar : PubMed/NCBI

20 

Rovetta F, Stacchiotti A, Faggi F, Catalani S, Apostoli P, Fanzani A and Aleo MF: Cobalt triggers necrotic cell death and atrophy in skeletal C2C12 myotubes. Toxicol Appl Pharmacol. 271:196–205. 2013. View Article : Google Scholar : PubMed/NCBI

21 

Rockwell S, Dobrucki IT, Kim EY, Marrison ST and Vu VT: Hypoxia and radiation therapy: Past history, ongoing research, and future promise. Curr Mol Med. 9:442–458. 2009. View Article : Google Scholar : PubMed/NCBI

22 

Begg AC, Stewart FA and Vens C: Strategies to improve radiotherapy with targeted drugs. Nat Rev Cancer. 11:239–253. 2011. View Article : Google Scholar : PubMed/NCBI

23 

Moeller BJ and Dewhirst MW: HIF-1 and tumour radiosensitivity. Br J Cancer. 95((1)): 1–5. 2006.(Epub ahead of print). View Article : Google Scholar : PubMed/NCBI

24 

Kaanders JH, Bussink J and van der Kogel AJ: ARCON: A novel biology-based approach in radiotherapy. Lancet Oncol. 3:728–737. 2002. View Article : Google Scholar : PubMed/NCBI

25 

Li Z, Xie Y, Sheng W, Miao J, Xiang J and Yang J: Tumor-suppressive effect of adenovirus-mediated inhibitor of growth 4 gene transfer in breast carcinoma cells in vitro and in vivo. Cancer Biother Radiopharm. 25:427–437. 2010. View Article : Google Scholar : PubMed/NCBI

26 

Du Y, Cheng Y and Su G: The essential role of tumor suppressor gene ING4 in various human cancers and non-neoplastic disorders. Biosci Rep. 39:BSR201807732019. View Article : Google Scholar : PubMed/NCBI

27 

Xie Y, Zhang H, Sheng W, Xiang J, Ye Z and Yang J: Adenovirus-mediated ING4 expression suppresses lung carcinoma cell growth via induction of cell cycle alteration and apoptosis and inhibition of tumor invasion and angiogenesis. Cancer Lett. 271:105–116. 2008. View Article : Google Scholar : PubMed/NCBI

28 

You Q, Wang XS, Fu SB and Jin XM: Downregulated expression of inhibitor of growth 4 (ING4) in advanced colorectal cancers: A non-randomized experimental study. Pathol Oncol Res. 17:473–477. 2011. View Article : Google Scholar : PubMed/NCBI

29 

Wang QS, Li M, Zhang LY, Jin Y, Tong DD, Yu Y, Bai J, Huang Q, Liu FL, Liu A, et al: Down-regulation of ING4 is associated with initiation and progression of lung cancer. Histopathology. 57:271–281. 2010. View Article : Google Scholar : PubMed/NCBI

30 

Galal El-Shemi A, Mohammed Ashshi A, Oh E, Jung BK, Basalamah M, Alsaegh A and Yun CO: Efficacy of combining ING4 and TRAIL genes in cancer-targeting gene virotherapy strategy: First evidence in preclinical hepatocellular carcinoma. Gene Ther. 25:54–65. 2018. View Article : Google Scholar : PubMed/NCBI

31 

Zhang H, Zhou X, Xu C, Yang J, Xiang J, Tao M and Xie Y: Synergistic tumor suppression by adenovirus-mediated ING4/PTEN double gene therapy for gastric cancer. Cancer Gene Ther. 23:13–23. 2016. View Article : Google Scholar : PubMed/NCBI

32 

Wang Y, Yang J, Sheng W, Xie Y and Liu J: Adenovirus-mediated ING4/PTEN double tumor suppressor gene co-transfer modified by RGD enhances antitumor activity in human nasopharyngeal carcinoma cells. Int J Oncol. 46:1295–1303. 2015. View Article : Google Scholar : PubMed/NCBI

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Copy and paste a formatted citation
Spandidos Publications style
Ma T, Guo R, Wang X, Shen W, Zhu M, Jin Y and Xu H: Lentiviral vector with a radiation‑inducible promoter, carrying the ING4 gene, mediates radiosensitization controlled by radiotherapy in cervical cancer cells. Oncol Lett 21: 67, 2021.
APA
Ma, T., Guo, R., Wang, X., Shen, W., Zhu, M., Jin, Y., & Xu, H. (2021). Lentiviral vector with a radiation‑inducible promoter, carrying the ING4 gene, mediates radiosensitization controlled by radiotherapy in cervical cancer cells. Oncology Letters, 21, 67. https://doi.org/10.3892/ol.2020.12328
MLA
Ma, T., Guo, R., Wang, X., Shen, W., Zhu, M., Jin, Y., Xu, H."Lentiviral vector with a radiation‑inducible promoter, carrying the ING4 gene, mediates radiosensitization controlled by radiotherapy in cervical cancer cells". Oncology Letters 21.1 (2021): 67.
Chicago
Ma, T., Guo, R., Wang, X., Shen, W., Zhu, M., Jin, Y., Xu, H."Lentiviral vector with a radiation‑inducible promoter, carrying the ING4 gene, mediates radiosensitization controlled by radiotherapy in cervical cancer cells". Oncology Letters 21, no. 1 (2021): 67. https://doi.org/10.3892/ol.2020.12328
Copy and paste a formatted citation
x
Spandidos Publications style
Ma T, Guo R, Wang X, Shen W, Zhu M, Jin Y and Xu H: Lentiviral vector with a radiation‑inducible promoter, carrying the ING4 gene, mediates radiosensitization controlled by radiotherapy in cervical cancer cells. Oncol Lett 21: 67, 2021.
APA
Ma, T., Guo, R., Wang, X., Shen, W., Zhu, M., Jin, Y., & Xu, H. (2021). Lentiviral vector with a radiation‑inducible promoter, carrying the ING4 gene, mediates radiosensitization controlled by radiotherapy in cervical cancer cells. Oncology Letters, 21, 67. https://doi.org/10.3892/ol.2020.12328
MLA
Ma, T., Guo, R., Wang, X., Shen, W., Zhu, M., Jin, Y., Xu, H."Lentiviral vector with a radiation‑inducible promoter, carrying the ING4 gene, mediates radiosensitization controlled by radiotherapy in cervical cancer cells". Oncology Letters 21.1 (2021): 67.
Chicago
Ma, T., Guo, R., Wang, X., Shen, W., Zhu, M., Jin, Y., Xu, H."Lentiviral vector with a radiation‑inducible promoter, carrying the ING4 gene, mediates radiosensitization controlled by radiotherapy in cervical cancer cells". Oncology Letters 21, no. 1 (2021): 67. https://doi.org/10.3892/ol.2020.12328
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