Skip to main content
Log in

Inhibitory effects of transfected Bcl-XL antisense oligodeoxynucleotide to proliferation and growth in esophageal carcinoma cell line and human esophageal carcinoma xenograft of nude mice

  • Published:
The Chinese-German Journal of Clinical Oncology

Abstract

Objective

The aim of our study was to investigate the biological effects of Bcl-XL antisense oligodeoxynucleotide (ASODN) transfected into cultured esophageal carcinoma cells and human esophageal carcinoma xenograft in nude mice.

Methods

Cationic liposome-mediated ASODN was used to transfect esophageal carcinoma cells. RT-PCR, Western blot, MTT assay, flow cytometry, and in situ apoptosis cells detection (TUNEL detection) were used to systematically study the biological effects of transfected cells both in vitro and in vivo.

Results

In this study, the results showed that the proliferation of esophageal carcinoma cells in ASODN group decreased significantly when compared with the control group (P < 0.05), at 57.3% Bcl-XL mRNA inhibitory rate, and a significant decreasing of Bcl-XL protein expression, at the apoptosis rates of (31.1 ± 5.8)% and 35.0% by flow cytometry and TUNEL assay respectively (P < 0.01, when compared with control groups). It also showed that the growth of human esophageal carcinoma in nude mice of ASODN group was significantly inhibited (P < 0.05), together with a significant decreased expression level of Bcl-XL mRNA and protein, and an induced tumor cell apoptosis in nude mice.

Conclusion

Our result indicates Bcl-XL ASODN can effectively inhibit the proliferation of esophageal carcinoma cells in vitro and tumor growth in vivo. The suppression of Bcl-XL expression by ASODN may offer both a therapeutic approach and an important theoretic foundation for gene therapy against esophageal carcinoma.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. Krecicki T, Fraczek M, Kozlak J, et al. Bcl-XL protein expression in laryngeal squamous cell carcinoma. Clin Otolaryngol Allied Sci, 2004, 29: 55–58.

    Article  CAS  PubMed  Google Scholar 

  2. Zhao WL, Daneshpouy ME, Mounier N, et al. Prognostic significance of bcl-xL gene expression and apoptotic cell counts in follicular lymphoma. Blood, 2004, 103: 695–697.

    Article  CAS  PubMed  Google Scholar 

  3. Leech SH, Olie RA, Gautschi O, et al. Induction of apoptosis in lungcancer cells following Bcl-XL, anti-sense treatment. Int J Cancer, 2000, 86: 570–576.

    Article  CAS  PubMed  Google Scholar 

  4. Lin WM. Guide of operation and application on PCR technic. Beijing: Science Technic Publishing House of China, 1991. 69–72.

    Google Scholar 

  5. Arriola EL, Rodriguez-Lopez AM, Hickman JA, et al. Bcl-2 overexpression results in reciprocal downregulation of Bcl-X(L) and sensitized human testicular germ cell tumours to chemotherapy-induced apoptosis. Oncogene, 1999, 18: 1457–1464.

    Article  CAS  PubMed  Google Scholar 

  6. Mizutani Y, Kamoi K, Ukimura O, et al. Synergistic cytotoxicity and apoptosis of JTE-522, a selective cyclooxygenase-2 inhibitor, and 5-fluorouracil against bladder cancer. J Urol, 2002, 168: 2650–2654.

    Article  CAS  PubMed  Google Scholar 

  7. Wang T, Chen F, Chen Z. Honokiol induces apoptosis through p53-independent pathway in human colorectal line RKO. World J Gastroenterol, 2004, 10:2205–2208.

    CAS  PubMed  Google Scholar 

  8. Watanabe J, Kushihata F, Honda K, et al. Prognostic significance of Bcl-xL in human hepatocellular carcinoma. Surgery, 2004, 135: 604–612.

    Article  PubMed  Google Scholar 

  9. Chu R, Upreti M, Ding WX, et al. Regulation of Bax by C-Jun NH2-terminal kinase and Bcl-xL in vinblastine-induced apoptosis. Biochem Pharmacol, 2009, 78: 241–248.

    Article  CAS  PubMed  Google Scholar 

  10. Wang X, Xing D, Liu L, et al. BimL directly neutralizes Bcl-xL to promote Bax activation during UV-induced apoptosis. FEBS Lett, 2009, 583: 1873–1879.

    Article  CAS  PubMed  Google Scholar 

  11. Soltani-Arabshahi R, Leboeuf C, Rivet J, et al. Bcl-xL gene expression correlated with lower apoptotic cell numbers and shorter progressionfree survival in PCFCL. J Invest Dermatol, 2009, 129: 1703–1709.

    Article  CAS  PubMed  Google Scholar 

  12. Xing LN, Qi L. Effects of antisense oligonucleotides targeting VEGF on radio sensitivity of uterine cervix cancer Hela cells. Chinese-German J Clin Oncol, 2009, 8: 50–54.

    Article  CAS  Google Scholar 

  13. Okumura M, Kajiyama Y, Takeda K, et al. Correlation between loss of Bcl-XL expression and improved prognosis in advanced esophageal cancer treated by preoperative chemoradiotherapy. Eur Surg Res, 2008, 41: 260–266.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Lei Zhang.

Additional information

Supported by a grant from the Henan Innovation Project for University Prominent Research Talents (No. 2007KYCX005).

Rights and permissions

Reprints and permissions

About this article

Cite this article

Zhang, L., Wen, H., Zhang, L. et al. Inhibitory effects of transfected Bcl-XL antisense oligodeoxynucleotide to proliferation and growth in esophageal carcinoma cell line and human esophageal carcinoma xenograft of nude mice. Chin. -Ger. J. Clin. Oncol. 9, 169–174 (2010). https://doi.org/10.1007/s10330-010-0006-x

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10330-010-0006-x

Key words

Navigation