[MDR-reversing effect of short peptide binding specifically to multidrug-resistant gastric cancer cells]

Zhonghua Zhong Liu Za Zhi. 2007 Apr;29(4):258-61.
[Article in Chinese]

Abstract

Objective: To investigate the binding effect of the short peptide SY1 to the multidrug-resistant gastric cancer cell line SGC7901/VCR cells and its reversing effect on those cancer cells.

Methods: The cultured cells were divided into two groups named SGC7901 and SGC7901/VCR. The SGC7901/VCR group was co-cultured with vincristine (VCR). SY1 was obtained from cyclic 7-mer peptide library by differential screening. Immunofluorescence technique was used to detect the capacity of SY1-containing positive phage specifically binding to SGC7901/VCR cells, compared with that of the negative phage and unrelated phage. MTT assay in vitro was performed to analyze the alteration of drug resistance of SGC7901/ VCR cells, using the positive phages and the chemically synthesized SY1 peptide. Flow cytometry assay was performed to detect the accumulation and retention of adriamycin (ADM) in the SGC7901/VCR cells.

Results: Immunofluorescence analysis showed that the SY1-containing positive phages could bind to the SGC7901/VCR cell surface but not to its parent cell line SGC7901 cells. The unrelated phage and negative phage did not bind to SGC7901/VCR cells. These results indicated that SY1 could specifically bind to SGC7901/VCR cells. MTT assay in vitro showed that the survival rate of SGC7901/VCR cells was reduced considerably by the positive phages and the chemically synthesized SY1 peptide (P <0. 05), indicating that SY1 enhanced the sensitivity of SGC7901/VCR cells to chemotherapeutic drug VCR. Flow-cytometric detection showed that SY1 enhanced the accumulation of ADM in the SGC7901/VCR cells, compared with that of the negative phages and the unrelated phages (P <0.05).

Conclusion: SY1 not only is able to bind to SGC7901/VCR cells specifically, but also can partly reverse the resistance of SGC7901/VCR cell line to chemotherapeutic drug VCR. Those findings might be important to open a new approach to reverse the gastric cancer MDR.

Publication types

  • English Abstract

MeSH terms

  • Adenocarcinoma / genetics
  • Adenocarcinoma / metabolism
  • Adenocarcinoma / pathology
  • Antibiotics, Antineoplastic / pharmacology
  • Antineoplastic Agents, Phytogenic / pharmacology
  • Bacteriophages / genetics
  • Binding Sites
  • Cell Line, Tumor
  • Cell Membrane / metabolism
  • Cell Survival / drug effects
  • Doxorubicin / pharmacology
  • Drug Resistance, Multiple*
  • Drug Resistance, Neoplasm*
  • Flow Cytometry
  • Fluorescent Antibody Technique
  • Humans
  • Peptide Library
  • Peptides, Cyclic / genetics
  • Peptides, Cyclic / metabolism*
  • Protein Binding
  • Stomach Neoplasms / genetics
  • Stomach Neoplasms / metabolism
  • Stomach Neoplasms / pathology
  • Vincristine / pharmacology

Substances

  • Antibiotics, Antineoplastic
  • Antineoplastic Agents, Phytogenic
  • Peptide Library
  • Peptides, Cyclic
  • Vincristine
  • Doxorubicin