rAd-p53 enhances the sensitivity of human gastric cancer cells to chemotherapy.

Abstract

AIM:

To investigate potential antitumor effects of rAd-p53 by determining if it enhanced sensitivity of gastric cancer cells to chemotherapy.

METHODS:

Three gastric cancer cell lines with distinct levels of differentiation were treated with various doses of rAd-p53 alone, oxaliplatin (OXA) alone, or a combination of both. Cell growth was assessed with an 3-(4,5)-dimethylthiahiazo (-z-y1)-3,5-diphenytetrazoliumromide assay and the expression levels of p53, Bax and Bcl-2 were determined by immunohistochemistry. The presence of apoptosis and the expression of caspase-3 were determined using flow cytometry.

RESULTS:

Treatment with rAd-p53 or OXA alone inhibited gastric cancer cell growth in a time- and dose-dependent manner; moreover, significant synergistic effects were observed when these treatments were combined. Immunohistochemical analysis demonstrated that treatment with rAd-p53 alone, OXA alone or combined treatment led to decreased Bcl-2 expression and increased Bax expression in gastric cancer cells. Furthermore, flow cytometry showed that rAd-p53 alone, OXA alone or combination treatment induced apoptosis of gastric cancer cells, which was accompanied by increased expression of caspase-3.

CONCLUSION:

rAd-p53 enhances the sensitivity of gastric cancer cells to chemotherapy by promoting apoptosis. Thus, our results suggest that p53 gene therapy combined with chemotherapy represents a novel avenue for gastric cancer treatment.

• Authors: Guang-Xia Chen, Li-Hong Zheng, Shi-Yu Liu, Xiao-Hua He
• Journal: World journal of gastroenterology (World J Gastroenterol) Vol. 17 Issue 38 Pg. 4289-97 (Oct 14 2011) ISSN: 2219-2840 [Electronic] United States
• PMID: 22090785 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents
• Organoplatinum Compounds
• Proto-Oncogene Proteins c-bcl-2
• Tumor Suppressor Protein p53
• bcl-2-Associated X Protein
• Oxaliplatin
• Caspase 3

Topics

• Adenoviridae (genetics, metabolism)
• Antineoplastic Agents (therapeutic use)
• Apoptosis (physiology)
• Caspase 3 (metabolism)
• Cell Line, Tumor
• Combined Modality Therapy
• Dose-Response Relationship, Drug
• Genetic Therapy (methods)
• Humans
• Organoplatinum Compounds (therapeutic use)
• Oxaliplatin
• Proto-Oncogene Proteins c-bcl-2 (metabolism)
• Stomach Neoplasms (drug therapy, metabolism, pathology)
• Tumor Suppressor Protein p53 (genetics, metabolism)
• bcl-2-Associated X Protein (metabolism)