Dynamic changes and surveillance function of prion protein expression in gastric cancer drug resistance

World J Gastroenterol. 2011 Sep 21;17(35):3986-93. doi: 10.3748/wjg.v17.i35.3986.

Abstract

Aim: To explore the dynamic changes of prion protein (PrPc) in the process of gastric cancer drug resistance and the role of PrPc expression in the prognosis of gastric cancer patients receiving chemotherapy.

Methods: A series of gastric cancer cell lines resistant to different concentrations of adriamycin was established, and the expression of PrPc, Bcl-2 and Bax was detected in these cells. Apoptosis was determined using Annexin V staining. Western blotting and immunohistochemistry were performed to detect the expression of PrPc in patients receiving chemotherapy and to explore the role of PrPc expression in predicting the chemosensitivity and the outcome of gastric cancer patients receiving chemotherapy. Follow-up was performed for 2 years.

Results: PrPc expression was increased with the increase in drug resistance. Bcl-2, together with PrPc, increased the level of anti-apoptosis of cancer cells. Increased PrPc expression predicted the enhanced level of anti-apoptosis and resistance to anticancer drugs. PrPc expression could be used as a marker for predicting the efficacy of chemotherapy and the prognosis of gastric cancer. Increased PrPc expression predicted both poor chemosensitivity and a low 2-year survival rate. Contrarily, low PrPc expression predicted favorable chemosensitivity and a relatively high 2-year survival rate.

Conclusion: PrPc expression is associated with histological types and differentiation of gastric cancer cells; The PrPc expression level might be a valuable marker in predicting the efficacy of chemotherapy and the prognosis of gastric cancer patients receiving chemotherapy.

Keywords: Apoptosis; Chemotherapy; Drug resistance; Gastric cancer; Prion protein.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Animals
  • Antineoplastic Agents / therapeutic use
  • Apoptosis
  • Cell Line, Tumor
  • Doxorubicin / therapeutic use
  • Drug Resistance, Neoplasm / physiology*
  • Female
  • Humans
  • Male
  • Microarray Analysis
  • Middle Aged
  • PrPC Proteins / metabolism*
  • Prognosis
  • Proto-Oncogene Proteins c-bcl-2 / metabolism
  • Stomach Neoplasms / diagnosis
  • Stomach Neoplasms / drug therapy
  • Stomach Neoplasms / metabolism*
  • Stomach Neoplasms / physiopathology*
  • bcl-2-Associated X Protein / metabolism

Substances

  • Antineoplastic Agents
  • PrPC Proteins
  • Proto-Oncogene Proteins c-bcl-2
  • bcl-2-Associated X Protein
  • Doxorubicin