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.

  • Article
  • Published:

Downregulation of liver–intestine cadherin enhances cisplatin-induced apoptosis in human gastric cancer BGC823 cells

Abstract

Gastric cancer is the fourth most common type of cancer. Liver–intestine cadherin (CDH17) has been found to be involved in the proliferation and apoptosis of gastric cancer cells. Cisplatin is one of the most widely used antineoplastic agents in the treatment of solid tumor and hematological malignancies. However, the mechanism of enhancing cisplatin-inducing effects on human gastric cancer BGC823 cells by blocking CDH17 gene, both in vitro and in vivo, remains to be clarified. In this study, we investigated the signaling pathway by which cisplatin induces apoptosis by blocking CDH17 gene in gastric cancer BGC823 cells. Our results indicate that down-expression of CDH17 gene can enhance apoptosis-inducing effects of cisplatin on human gastric cancer BGC823 cells. The expression levels of Bax and Cyt-c proteins were upregulated, but the expression levels of Bcl-2 and Bcl-xL proteins were downregulated by blocking CDH17 gene in gastric cancer BGC823 cells after treatment with cisplatin. Moreover, down-expression of CDH17 enhanced the efficacy of cisplatin-induced inhibition of tumor growth in nude mice via apoptosis induction. Down-expression of CDH17 gene can significantly improve apoptosis-inducing effects of cisplatin in vitro and in vivo, which is a new strategy to improve chemotherapeutic effects on gastric cancer.

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

Fig.1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

  1. Sugano K. Screening of gastric cancer in Asia. Best Pract Res Clin Gastroenterol. 2015;29:895–905.

    Article  PubMed  Google Scholar 

  2. Parkin DM, Bray F, Ferlay J, Pisani P. Global cancer statistics. 2002. CA Cancer J Clin. 2005;55:74–108.

    Article  PubMed  Google Scholar 

  3. Winer E, Gralow J, Diller L, Karlan B, Loehrer P, Pierce L, et al. Clinical cancer advances 2008: major research advances in cancer treatment, prevention, and screening—a report from the American Society of Clinical Oncology. J Clin Oncol. 2009;27:812–26.

    Article  PubMed  Google Scholar 

  4. Bozzetti F, Marubini E, Bonfanti G, Miceli R, Piano C, Gennari L. Subtotal versus total gastrectomy for gastric cancer: five-year survival rates in a multicenter randomized Italian trial. Ann Surg. 1999;230:170–8.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  5. Uña E. Gastric cancer: predictors of recurrence when lymph-node dissection is inadequate. World J Surg Oncol. 2009;7:69.

    Article  PubMed  PubMed Central  Google Scholar 

  6. Gessner R, Tauber R. Intestinal cell adhesion molecules. Liver–intestine cadherin. Ann N Y Acad Sci. 2000;915:136–43.

    Article  PubMed  CAS  Google Scholar 

  7. Grötzinger C, Kneifel J, Patschan D, Schnoy N, Anagnostopoulos I, Faiss S, et al. LI-cadherin: a marker of gastric metaplasia and neoplasia. Gut 2001;49:73–81.

    Article  PubMed  PubMed Central  Google Scholar 

  8. Dong WG, Yu QF, Xu Y, Fan LF. Li-cadherin is inversely correlated with galectin-3 expression ingastric cancer. Dig Dis Sci. 2008;53:1811–7.

    Article  PubMed  CAS  Google Scholar 

  9. Dong W, Yu Q, Xu Y. Altered expression of a Li-cadherin in gastric cancer and intestinal metaplasia. Dig Dis Sci. 2007;52:536–42.

    Article  PubMed  CAS  Google Scholar 

  10. Berndorff D, Gessner R, Kreft B, Schnoy N, Lajous-Petter AM, Loch N, et al. Liver-intestine cadherin: molecular cloning and characterization of a novel Ca(2+)-dependent cell adhesion molecule expressed in liver and intestine. J Cell Biol. 1994;125:1353–69.

    Article  PubMed  CAS  Google Scholar 

  11. Hinoi T, Lucas PC, Kuick R, Hanash S, Cho KR, Fearon ER. CDX2 regulates liver intestine-cadherin expression in normal and malignant colon epithelium and intestinal metaplasia. Gastroenterology 2002;123:1565–77.

    Article  PubMed  CAS  Google Scholar 

  12. Takamura M, Ichida T, Matsuda Y, Kobayashi M, Yamagiwa S, Genda T, et al. Reduced expression of liver-intestine cadherin is associated with progression and lymph node metastasis of human colorectal carcinoma. Cancer Lett. 2004;212:253–9.

    Article  PubMed  CAS  Google Scholar 

  13. Kwak JM, Min BW, Lee JH, Choi JS, Lee SI, Park SS, et al. The prognostic significance of E-cadherin and liver intestine-cadherin expression in colorectal cancer. Dis Colon Rectum 2007;50:1873–80.

    Article  PubMed  Google Scholar 

  14. Boo YJ, Park JM, Kim J, Chae YS, Min BW, Um JW, et al. L1 expression as a marker for poor prognosis, tumor progression, and short survival in patients with colorectal cancer. Ann Surg Oncol. 2007;14:1703–11.

    Article  PubMed  Google Scholar 

  15. Kim BR, Shim JW, Sung DK, Kim SS, Jeon GW, Kim MJ, et al. Granulocyte stimulating factor attenuates hypoxic-ischemic brain injury by inhibiting apoptosis in neonatal rats. Yonsei Med J. 2008;49:836–42.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  16. Liu M, Luo XJ, Liao F, Lei XF, Dong WG. Noscapine induces mitochondria-mediated apoptosis in gastric cancer cells in vitro and in vivo. Cancer Chemoth Pharm. 2011;67:605–12.

    Article  CAS  Google Scholar 

  17. Suzuki H, Iwasaki E, Hibi T. Helicobacter pylori and gastric cancer. Gastric Cancer 2009;12:79–87.

    Article  PubMed  Google Scholar 

  18. Digklia A, Wagner AD. Advanced gastric cancer: current treatment landscape and future perspectives. World J Gastroenterol. 2016;22:2403.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  19. Boller K, Vestweber D, Kemler R. Cell-adhesion molecule uvomorulin is localized in the intermediate junctions of adult intestinal epithelial cells. J Cell Biol. 1985;100:327–32.

    Article  PubMed  CAS  Google Scholar 

  20. Gumbiner B, Simons K. A functional assay for proteins involved in establishing an epithelial occluding barrier: identification of a uvomorulin-like polypeptide. J Cell Biol. 1986;102:457–68.

    Article  PubMed  CAS  Google Scholar 

  21. Gumbiner B, Simons K. The role of uvomorulin in the formation of epithelial occluding junctions. Ciba Found Symp. 1987;125:168–86.

    PubMed  CAS  Google Scholar 

  22. Takamura M, Sakamoto M, Ino Y, Shimamura T, Ichida T, Asakura H, et al. Expression of liver intestine cadherin and its possible interaction with galectin-3 in ductal adenocarcinoma of the pancreas. Cancer Sci. 2003;94:425–30.

    Article  PubMed  CAS  Google Scholar 

  23. Hinoi T, Lucas PC, Kuick R, Hanash S, Cho KR, Fearon ER. CDX2 regulates liver–intestine cadherin expression in normal and malignant colon epithelium and intestinal metaplasia. Gastroenterology 2002;123:1565–77.

    Article  PubMed  CAS  Google Scholar 

  24. Takamura M, Ichida T, Matsuda Y, Kobayashi M, Yamagiwa S, Genda T, et al. Reduced expression of liver intestine cadherin is associated with progression and lymph node metastasis of human colorectal carcinoma. Cancer Lett. 2004;212:253–59.

    Article  PubMed  CAS  Google Scholar 

  25. Krysko DV, Berghe TV, D’Herde K, e Vandenabeele P. Apoptosis and necrosis: detection, discrimination and phagocytosis. Methods 2008;44:205–21.

    Article  PubMed  CAS  Google Scholar 

  26. Tsujimoto Y, Finger LR, Yunis J, Nowell PC, Croce CM. Cloning of the chromosome breakpoint of neoplastic B cells with the t (14;18) chromosome translocation. Science 1984;226:1097–99.

    Article  PubMed  CAS  Google Scholar 

  27. Jourdain A, Martinou JC. Mitochondrial outer-membrane permeabilization and remodeling in apoptosis. Int J Biochem Cell Biol. 2009;41:1884–9.

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgements

This work was supported by Wuhan Science and Technology Bureau of applied basic research projects (2015060101010064), Hubei Province Natural Science Foundation of China (2013CFB358), and Project of Health and Family Planning Commission of Wuhan Municipality (WX15C09 and WX14C18). We sincerely thank Dr. Wei Guo Dong and Mr. Hong Xia from the Institute of Gastroenterology and Hepatology, Renmin Hospital of Wuhan University.

Author information

Authors and Affiliations

Authors

Corresponding authors

Correspondence to Xia Tian or Xiaodong Huang.

Ethics declarations

Conflict of interest

The authors declare that they have no competing interests.

Additional information

Meng Liu and Zheng Han contributed equally to this work.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Liu, M., Han, Z., Zhu, QX. et al. Downregulation of liver–intestine cadherin enhances cisplatin-induced apoptosis in human gastric cancer BGC823 cells. Cancer Gene Ther 25, 1–9 (2018). https://doi.org/10.1038/s41417-017-0001-2

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41417-017-0001-2

Search

Quick links