Suppressing the growth of rectal cancer xenografts derived from patient tumors by an adenovector expressing small hairpin RNA targeting Bcl-XL

J Gene Med. 2012 Dec;14(12):761-8. doi: 10.1002/jgm.2681.

Abstract

Background: Bcl-XL, a mitochondria membrane protein, is overexpressed in colorectal cancers and promotes cell survival. We have previously shown that the adenovector expressing small hairpin (sh)RNA targeting Bcl-XL could induce significantly apoptosis in colon cancer cells. In the present study, we aimed to further detect the anti-cancer effect of adenovector expressing the shRNA targeting Bcl-XL (Ad/Bcl-XL shRNA) on rectal cancer xenografts that were derived from patient tumors.

Methods: We first established three rectal cancer xenografts. These xenografts were subsequently treated with Ad/Bcl-XL shRNA alone or in combination with 5-fluouracil (5-Fu). Finally, the inhibition of tumor growth, survival time and induction of apoptosis were analyzed.

Results: The results obtained demonstrated that Ad/Bcl-XL shRNA could effectively suppress the tumor growth of all three rectal cancer xenografts and prolong their survival time. After being combined with 5-Fu, the suppressing effect of Ad/Bcl-XL shRNA was enhanced further. In addition, the data also showed that Ad/Bcl-XL shRNA combined with 5-Fu could significantly increase the apoptotic ratio in the rectal cancer xenograft.

Conclusions: These data indicate that Ad/Bcl-XL shRNA with or without 5-Fu has effective anti-tumor effects on the patient tumor-derived rectal cancer xenografts, suggesting that it could be a potential strategy for rectal cancer therapy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenoviridae / genetics*
  • Animals
  • Antineoplastic Agents / administration & dosage
  • Gene Expression
  • Genetic Vectors
  • Humans
  • Mice
  • Mice, Nude
  • RNA, Small Interfering / genetics*
  • RNA, Small Interfering / metabolism
  • Rectal Neoplasms / mortality
  • Rectal Neoplasms / pathology
  • Rectal Neoplasms / therapy*
  • Tumor Burden / drug effects
  • Tumor Burden / genetics
  • Xenograft Model Antitumor Assays
  • bcl-X Protein / antagonists & inhibitors*
  • bcl-X Protein / genetics

Substances

  • Antineoplastic Agents
  • RNA, Small Interfering
  • bcl-X Protein