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Effect of ZNRD1 gene antisense RNA on drug resistant gastric cancer cells

Yu-Mei Zhang1, Yan-Qiu Zhao, Yang-Lin Pan

  • 1Department of Gastroenterology, Xijing Hospital, Fourth Military Medical University, Xi'an 710033, Shaanxi Province, China.

World Journal of Gastroenterology
|April 30, 2003
PubMed
Abstract

Insights

The ZNRD1 gene is highly expressed in multidrug-resistant gastric cancer cells. Targeting ZNRD1 with antisense nucleic acid can sensitize these cells to chemotherapy, increasing drug accumulation and inhibiting proliferation.

Area of Science:

  • Molecular Biology
  • Cancer Research
  • Genetics

Background:

  • Gastric cancer often develops multidrug resistance (MDR).
  • The ZNRD1 gene's role in gastric cancer MDR is not fully understood.
  • Investigating ZNRD1 expression is crucial for understanding drug resistance mechanisms.

Purpose of the Study:

  • To quantify ZNRD1 gene expression in gastric cancer cells and their multidrug-resistant counterparts.
  • To evaluate the therapeutic potential of ZNRD1 antisense nucleic acid in reversing MDR in gastric cancer cells.
  • To assess the impact of ZNRD1 inhibition on cell cycle, drug accumulation, and proliferation.

Main Methods:

  • ZNRD1 gene amplification and mRNA expression analysis via RT-PCR.
  • Construction and transfection of ZNRD1 antisense expression vector into SGC7901/VCR cells.
  • Immunochemical detection of ZNRD1 protein levels.
  • Flow cytometry (FACS) for cell cycle analysis and intracellular adriamycin (ADM) accumulation.
  • MTT assay for cell proliferation and vincristine (VCR) sensitization.

Main Results:

  • ZNRD1 expression was significantly higher in multidrug-resistant SGC7901/VCR cells compared to SGC7901 cells.
  • Transfection with ZNRD1 antisense nucleic acid effectively reduced ZNRD1 protein expression.
  • Antisense ZNRD1 treatment led to G1 cell cycle arrest and increased intracellular ADM accumulation.
  • MTT assays demonstrated reduced proliferation and enhanced sensitivity to VCR in ZNRD1-inhibited cells.

Conclusions:

  • High ZNRD1 expression is associated with vincristine resistance in gastric cancer cells.
  • ZNRD1 antisense nucleic acid effectively inhibits ZNRD1 protein expression.
  • ZNRD1 inhibition sensitizes drug-resistant gastric cancer cells to chemotherapy, enhances drug accumulation, and suppresses proliferation.
  • Targeting ZNRD1 offers a potential strategy to overcome MDR in gastric cancer.

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