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Open Access Research article

Therapeutic effects of lentivirus-mediated shRNA targeting of cyclin D1 in human gastric cancer

Jin-Hee Seo123, Eui-Suk Jeong12 and Yang-Kyu Choi12*

Author Affiliations

1 Department of Laboratory Animal Medicine, College of Veterinary Medicine, Konkuk University, Neungdong-ro, Gwangjin-gu, Seoul 143-701, Republic of Korea

2 Veterinary Science Research Institute, College of Veterinary Medicine, Konkuk University, Neungdong-ro, Gwangjin-gu, Seoul 143-701, Republic of Korea

3 Laboratory Animal Facility, Korea Institute of Radiological and Medical Sciences, Seoul 139-706, Republic of Korea

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BMC Cancer 2014, 14:175  doi:10.1186/1471-2407-14-175

Published: 11 March 2014

Abstract

Background

Gastric cancer is the second most common cause of cancer-related death in males and the fourth in females. Traditional treatment has poor prognosis because of recurrence and systemic side effects. Therefore, the development of new therapeutic strategies is an important issue. Lentivirus-mediated shRNA stably inhibits target genes and can efficiently transduce most cells. Since overexpressed cyclin D1 is closely related to human gastric cancer progression, inhibition of cyclin D1 using specific targeting could be an effective treatment method of human gastric cancer.

Methods

The therapeutic effect of lentivirus-mediated shRNA targeting of cyclin D1 (ShCCND1) was analyzed both in vitro and in vivo experiments.

Results

In vitro, NCI-N87 cells with downregulation of cyclin D1 by ShCCND1 showed significant inhibition of cell proliferation, cell motility, and clonogenicity. Downregulation of cyclin D1 in NCI-N87 cells also resulted in significantly increased G1 arrest and apoptosis. In vivo, stable NCI-N87 cells expressing ShCCND1 were engrafted into nude mice. Then, the cancer-growth inhibition effect of lentivirus was confirmed. To assess lentivirus including ShCCND1 as a therapeutic agent, intratumoral injection was conducted. Tumor growth of the lentivirus-treated group was significantly inhibited compared to growth of the control group. These results are in accordance with the in vitro data and lend support to the mitotic figure count and apoptosis analysis of the tumor mass.

Conclusion

The lentivirus-mediated ShCCND1 was constructed, which effectively inhibited growth of NCI-N87-derived cancer both in vitro and in vivo. The efficiency of shRNA knockdown and variation in the degree of inhibition is mediated by different shRNA sequences and cancer cell lines. These experimental results suggest the possibility of developing new gastric cancer therapies using lentivirus-mediated shRNA.

Keywords:
Gastric cancer; Cyclin D1; Lentivirus; shRNA