Bcl-XL small interfering RNA suppresses the proliferation of 5-fluorouracil-resistant human colon cancer cells

Hongbo Zhu, Wei Guo, Lidong Zhang, John J. Davis, Fuminori Teranishi, Shuhong Wu, Xiaobo Cao, Jonathan Daniel, W. Roy Smythe, Bingliang Fang

Research output: Contribution to journalArticle

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Abstract

5-Fluorouracil (5-FU) is commonly used to treat human colon cancers but resistance to this compound is frequently observed in clinics. To characterize mechanisms of resistance to 5-FU and to develop new strategies for overcoming it, we established two cell lines that were resistant to 5-FU but not other chemotherapeutic agents from parental 5-FU-sensitive cell lines. Western blot analysis revealed that these resistant cells overexpressed the proteins Bcl-XL, Bcl-Xs, and Bik, and further data showed that the cells were resistant to 5-FU-induced DNA damage and cell cycle disorder. However, in parental cells, enforced expression of Bcl-XL protein provided only limited protection from 5-FU-induced apoptosis and overexpression of Bcl-XL protein did not affect 5-FU-induced DNA damage or cell cycle changes; these findings suggested that overexpression of Bcl-XL protein was not the major contributor to 5-FU resistance in any of our cells lines. Even so, knockdown of Bcl-XL protein expression by Bcl-XL-specific small interfering RNA could inhibit proliferation more effectively in 5-FU-resistant cells than in 5-FU-sensitive cells, and the combination of Bcl-XL-specific small interfering RNA and 5-FU had additive effect on the inhibition of 5-FU-resistant cells. These results suggest that down-regulation of Bcl-XL protein expression might provide a new treatment strategy for human 5-FU-resistant colon cancer therapy.

Original languageEnglish
Pages (from-to)451-456
Number of pages6
JournalMolecular Cancer Therapeutics
Volume4
Issue number3
Publication statusPublished - Mar 1 2005
Externally publishedYes

Fingerprint

Fluorouracil
Colonic Neoplasms
Small Interfering RNA
bcl-X Protein
Cell Line
DNA Damage
Cell Cycle
Down-Regulation
Western Blotting
Apoptosis

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Bcl-XL small interfering RNA suppresses the proliferation of 5-fluorouracil-resistant human colon cancer cells. / Zhu, Hongbo; Guo, Wei; Zhang, Lidong; Davis, John J.; Teranishi, Fuminori; Wu, Shuhong; Cao, Xiaobo; Daniel, Jonathan; Smythe, W. Roy; Fang, Bingliang.

In: Molecular Cancer Therapeutics, Vol. 4, No. 3, 01.03.2005, p. 451-456.

Research output: Contribution to journalArticle

Zhu, H, Guo, W, Zhang, L, Davis, JJ, Teranishi, F, Wu, S, Cao, X, Daniel, J, Smythe, WR & Fang, B 2005, 'Bcl-XL small interfering RNA suppresses the proliferation of 5-fluorouracil-resistant human colon cancer cells', Molecular Cancer Therapeutics, vol. 4, no. 3, pp. 451-456.
Zhu, Hongbo ; Guo, Wei ; Zhang, Lidong ; Davis, John J. ; Teranishi, Fuminori ; Wu, Shuhong ; Cao, Xiaobo ; Daniel, Jonathan ; Smythe, W. Roy ; Fang, Bingliang. / Bcl-XL small interfering RNA suppresses the proliferation of 5-fluorouracil-resistant human colon cancer cells. In: Molecular Cancer Therapeutics. 2005 ; Vol. 4, No. 3. pp. 451-456.
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