Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Original Article
  • Published:

Prevention of tumor growth by needle-free jet injection of anti-C7orf24 siRNA

Abstract

Chromosome 7 open reading frame 24 (C7orf24), which was identified by proteome analysis, is upregulated in various types of cancer and is associated with cellular proliferation. However, in vivo antitumor effect by knockdown of C7orf24 has not been clarified. In this study, we investigated that the antitumor effect of anti-C7orf24 small interfering RNA (siRNA) administered by needle-free jet injection (JI) on lung cancer-bearing mice. Transfection of anti-C7orf24 siRNA induced cytotoxicity in cultured human lung cancer cells through specific knockdown of C7orf24. Furthermore, JI could effectively deliver anti-C7orf24 siRNA to tumor tissues, and as a result tumor growth was significantly inhibited. Immunohistochemical analysis revealed that C7orf24 levels were significantly reduced within tumor tissues collected from anti-C7orf24 siRNA-administered mice, indicating that the knockdown of C7orf24 induced cytotoxicity in tumor tissue. In conclusion, these data show for the first time that knockdown of C7orf24 prevents tumor growth in vivo following JI-mediated the siRNA delivery.

This is a preview of subscription content, access via your institution

Access options

Buy this article

Prices may be subject to local taxes which are calculated during checkout

Figure 1
Figure 2
Figure 3
Figure 4

Similar content being viewed by others

References

  1. Kageyama S, Iwaki H, Inoue H, Isono T, Yuasa T, Nogawa M et al. A novel tumor-related protein, C7orf24, identified by proteome differential display of bladder urothelial carcinoma. Proteomics Clin Appl 2007; 1: 192–199.

    Article  CAS  Google Scholar 

  2. Zhang C, Li HR, Fan JB, Wang-Rodriguez J, Downs T, Fu XD et al. Profiling alternatively spliced mRNA isoforms for prostate cancer classification. BMC Bioinformatics 2006; 7: 202.

    Article  Google Scholar 

  3. Gromov P, Gromova I, Friis E, Timmermans-Wielenga V, Rank F, Simon R et al. Proteomic profiling of mammary carcinomas identifies C7orf24, a gamma-glutamyl cyclotransferase, as a potential cancer biomarker. J Proteome Res 2010; 9: 3941–3953.

    Article  CAS  Google Scholar 

  4. Uejima D, Nishijo K, Kajita Y, Ishibe T, Aoyama T, Kageyama S et al. Involvement of cancer biomarker C7orf24 in the growth of human osteosarcoma. Anticancer Res 2011; 31: 1297–1305.

    CAS  PubMed  Google Scholar 

  5. Masuda Y, Maeda S, Watanabe A, Sano Y, Aiuchi T, Nakajo S et al. A novel 21-kDa cytochrome c-releasing factor is generated upon treatment of human leukemia U937 cells with geranylgeraniol. Biochem Biophys Res Commun 2006; 346: 454–460.

    Article  CAS  Google Scholar 

  6. Juliano R, Alam MR, Dixit V, Kang H . Mechanisms and strategies for effective delivery of antisense and siRNA oligonucleotides. Nucleic Acids Res 2008; 36: 4158–4171.

    Article  CAS  Google Scholar 

  7. Shim MS, Kwon YJ . Efficient and targeted delivery of siRNA in vivo. FEBS J 2010; 277: 4814–4827.

    Article  CAS  Google Scholar 

  8. Takei Y, Nemoto T, Mu P, Fujishima T, Ishimoto T, Hayakawa Y et al. In vivo silencing of a molecular target by short interfering RNA electroporation: tumor vascularization correlates to delivery efficiency. Mol Cancer Ther 2008; 7: 211–221.

    Article  CAS  Google Scholar 

  9. Kigasawa K, Kajimoto K, Hama S, Saito A, Kanamura K, Kogure K . Noninvasive delivery of siRNA into the epidermis by iontophoresis using an atopic dermatitis-like model rat. Int J Pharm 2010; 383: 157–160.

    Article  CAS  Google Scholar 

  10. Walther W, Stein U, Fichtner I, Malcherek L, Lemm M, Schlag PM . Nonviral in vivo gene delivery into tumors using a novel low volume jet-injection technology. Gene Ther 2001; 8: 173–180.

    Article  CAS  Google Scholar 

  11. Walther W, Siegel R, Kobelt D, Knösel T, Dietel M, Bembenek A et al. Novel jet-injection technology for nonviral intratumoral gene transfer in patients with melanoma and breast cancer. Clin Cancer Res 2008; 14: 7545–7553.

    Article  CAS  Google Scholar 

  12. Cartier R, Ren SV, Walther W, Stein U, Lewis A, Schlag PM et al. In vivo gene transfer by low-volume jet injection. Anal Biochem 2000; 282: 262–265.

    Article  CAS  Google Scholar 

  13. Kogure K, Manabe S, Hama S, Tokumura A, Fukuzawa K . Potentiation of anti-cancer effect by intravenous administration of vesiculated alpha-tocopheryl hemisuccinate on mouse melanoma in vivo. Cancer Lett 2003; 192: 19–24.

    Article  CAS  Google Scholar 

  14. Oakley AJ, Yamada T, Liu D, Coggan M, Clark AG, Board PG . The identification and structural characterization of C7orf24 as gamma-glutamyl cyclotransferase. An essential enzyme in the gamma-glutamyl cycle. J Biol Chem 2008; 283: 22031–22042.

    Article  CAS  Google Scholar 

  15. Taguchi K, Motohashi H, Yamamoto M . Molecular mechanisms of the Keap1-Nrf2 pathway in stress response and cancer evolution. Genes Cells 2011; 16: 123–140.

    Article  CAS  Google Scholar 

  16. Shibata T, Ohta T, Tong KI, Kokubu A, Odogawa R, Tsuta K et al. Cancer related mutations in NRF2 impair its recognition by Keap1-Cul3 E3 ligase and promote malignancy. Proc Natl Acad Sci USA 2008; 105: 13568–13573.

    Article  CAS  Google Scholar 

  17. Ohta T, Iijima K, Miyamoto M, Nakahara I, Tanaka H, Ohtsuji M et al. Loss of Keap1 function activates Nrf2 and provides advantages for lung cancer cell growth. Cancer Res 2008; 68: 1303–1309.

    Article  CAS  Google Scholar 

  18. Zhang P, Singh A, Yegnasubramanian S, Esopi D, Kombairaju P, Bodas M et al. Loss of Kelch-like ECH-associated protein 1 function in prostate cancer cells causes chemoresistance and radioresistance and promotes tumor growth. Mol Cancer Ther 2010; 9: 336–346.

    Article  CAS  Google Scholar 

  19. Jiang T, Chen N, Zhao F, Wang XJ, Kong B, Zheng W et al. High levels of Nrf2 determine chemoresistance in type II endometrial cancer. Cancer Res 2010; 70: 5486–5496.

    Article  CAS  Google Scholar 

  20. Shibata T, Saito S, Kokubu A, Suzuki T, Yamamoto M, Hirohashi S . Global downstream pathway analysis reveals a dependence of oncogenic NF-E2-related factor 2 mutation on the mTOR growth signaling pathway. Cancer Res 2010; 70: 9095–9105.

    Article  CAS  Google Scholar 

  21. Wakabayashi N, Shin S, Slocum SL, Agoston ES, Wakabayashi J, Kwak MK et al. Regulation of notch1 signaling by nrf2: implications for tissue regeneration. Sci Signal 2010; 3: 52.

    Article  Google Scholar 

  22. You A, Nam CW, Wakabayashi N, Yamamoto M, Kensler TW, Kwak MK . Transcription factor Nrf2 maintains the basal expression of Mdm2: an implication of the regulation of p53 signaling by Nrf2. Arch Biochem Biophys 2011; 507: 356–364.

    Article  CAS  Google Scholar 

  23. Hansen JM, Watson WH, Jones DP . Compartmentation of Nrf-2 redox control: regulation of cytoplasmic activation by glutathione and DNA binding by thioredoxin-1. Toxicol Sci 2004; 82: 308–317.

    Article  CAS  Google Scholar 

  24. Bos JD, Meinardi MM . The 500 Dalton rule for the skin penetration of chemical compounds and drugs. Exp Dermatol 2000; 9: 165–169.

    Article  CAS  Google Scholar 

  25. Tunggal JA, Helfrich I, Schmitz A, Schwarz H, Günzel D, Fromm M et al. E-cadherin is essential for in vivo epidermal barrier function by regulating tight junctions. EMBO J 2005; 24: 1146–1156.

    Article  CAS  Google Scholar 

  26. Grantab R, Sivananthan S, Tannock IF . The penetration of anticancer drugs through tumor tissue as a function of cellular adhesion and packing density of tumor cells. Cancer Res 2006; 66: 1033–1039.

    Article  CAS  Google Scholar 

  27. Juliano R, Alam MR, Dixit V, Kang H . Mechanisms and strategies for effective delivery of antisense and siRNA oligonucleotides. Nucleic Acids Res 2008; 36: 4158–4171.

    Article  CAS  Google Scholar 

  28. Kunugiza Y, Tomita N, Taniyama Y, Tomita T, Osako MK, Tamai K et al. Acceleration of wound healing by combined gene transfer of hepatocyte growth factor and prostacyclin synthase with Shima Jet. Gene Ther 2006; 13: 1143–1152.

    Article  CAS  Google Scholar 

Download references

Acknowledgements

This work was supported in part by the Japan Society for the Promotion of Science and by the Kyoto Pharmaceutical University Fund for the Promotion of Scientific Research.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to K Kogure.

Ethics declarations

Competing interests

The authors declare no conflict of interest.

Additional information

Supplementary Information accompanies the paper on Cancer Gene Therapy website

Supplementary information

Rights and permissions

Reprints and permissions

About this article

Cite this article

Hama, S., Arata, M., Nakamura, I. et al. Prevention of tumor growth by needle-free jet injection of anti-C7orf24 siRNA. Cancer Gene Ther 19, 553–557 (2012). https://doi.org/10.1038/cgt.2012.31

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/cgt.2012.31

Keywords

This article is cited by

Search

Quick links