Skip to main content

A New Inducible RNAi Model for Cancer Target Validation In Vivo

Background

Human xenograft tumor models are widely used for evaluation of potential cancer targets, by assessing the anti-tumor effects of specific agents, such as siRNA. siRNA is usually stably introduced into tumor cells prior to transplantation. However, oncogene silencing results in reduced cell growth/survival in vitro and/or failure to establish tumors in vivo, thus hindering tumor response-based efficacy evaluation that is more clinically relevant. We therefore explored a new tumor response model based on regulated RNAi.

Methods

A unique RNAi vector was generated to express shRNA only after induction with doxycylcine. Using this vector, we created a novel xenograft tumor model, in which tumors are established under non-induced conditions, followed by induced target inactivation upon oral dosing of the inducer. Three genes were evaluated, a known oncogene (mTOR), and two novel cancer targets (HE7 and HE26), by assessing the tumor response to their silencing.

Results

We demonstrate a significant response of staged tumor regression to silencing of all three target genes. For early staged tumors, inactivation of each of the three targets caused dramatic tumor regression (100% regressed and 50% became tumor-free for both mTOR and HE7, and 100% for HE26). Advanced staged tumors also demonstrated significant responses (100% regression for mTOR, and 75% for HE7, 85% HE26).

Conclusion

Our results demonstrate the utility of this unique and powerful model for efficacy evaluation of cancer targets; our data also provide robust in vivo efficacy validations of HE7 and HE26 as novel cancer therapeutic targets.

Author information

Affiliations

Authors

Corresponding author

Correspondence to F Wong-Staal.

Rights and permissions

Open Access This article is published under license to BioMed Central Ltd. This is an Open Access article is distributed under the terms of the Creative Commons Attribution License ( https://creativecommons.org/licenses/by/2.0 ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Reprints and Permissions

About this article

Cite this article

Li, Q., Ke, N., Zhou, D. et al. A New Inducible RNAi Model for Cancer Target Validation In Vivo. Retrovirology 2, S52 (2005). https://doi.org/10.1186/1742-4690-2-S1-S52

Download citation

Keywords

  • Tumor Response
  • Significant Response
  • Tumor Regression
  • Efficacy Evaluation
  • Regulate RNAi