Reversal of 5-flouroucial resistance by adenovirus-mediated transfer of wild-type p53 gene in multidrug-resistant human colon carcinoma LoVo/5-FU cells

World J Gastroenterol. 2004 Jul 1;10(13):1979-83. doi: 10.3748/wjg.v10.i13.1979.

Abstract

Aim: To observe the reversal effects of wide-type p53 gene on multi-drug resistance to 5-FU (LOVO/5-FU).

Methods: After treatment with Ad-p53, LOVO/5-FU sensitivity to 5-Fu was investigated using tetrazolium dye assay. Multidrug resistance gene-1 (MDR1) gene expression was assayed by semi-quantitative reverse transcription-polymerase chain reaction and the expression of p53 protein was examined by Western blotting.

Results: The reversal activity after treatment with wide-type p53 gene was increased up to 4.982 fold at 48 h. The expression of MDR1 gene decreased significantly after treatment with wide-type p53 gene, and the expression of p53 protein lasted for about 5 d, with a peak at 48 h, and began to decrease at 72 h.

Conclusion: Wide-type p53 gene has a remarkable reversal activity for the high expression of MDR1 gene in colorectal cancers. The reversal effects seem to be in a time dependent manner. It might have good prospects in clinical application.

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily B, Member 1 / genetics
  • Adenocarcinoma*
  • Adenoviridae / genetics
  • Antimetabolites, Antineoplastic / pharmacology*
  • Cell Division / drug effects
  • Colonic Neoplasms*
  • Drug Resistance, Multiple
  • Drug Resistance, Neoplasm
  • Fluorouracil / pharmacology*
  • Gene Expression Regulation, Neoplastic
  • Gene Transfer Techniques
  • Humans
  • Tumor Cells, Cultured
  • Tumor Suppressor Protein p53 / genetics*

Substances

  • ATP Binding Cassette Transporter, Subfamily B, Member 1
  • Antimetabolites, Antineoplastic
  • Tumor Suppressor Protein p53
  • Fluorouracil