PubMed · 2013 · 35 citations · 9 references
MedicineOncologyPharmacologyCancer PharmacologyChemotherapyMolecular OncologyApoptosis PharmacologyChemotherapy ResistanceCytotoxic ChemotherapyGastric CancerMetabolism Of Anticancer AgentsPharmacodynamics Of Anticancer AgentsAnticancer ChemotherapyBcl-2 InhibitionBcl-2 Protein ExpressionBcl-2 Protein RegulationCell Death AssaysChemoresistance In Gastric CancerChemotherapy-induced ApoptosisMetabolic Activity Assays
OBJECTIVE: To investigate chemoresistance of human gastric cancer to chemotherapeutic drugs in vitro and explore the relationship with Bcl-2 protein expression. METHODS: Single-cell suspensions were prepared from freshly excised samples of primary gastric cancer, and were separately exposed to taxol (TAX), cisplatin (CDDP), 5-fluorouracil (5-FU), adriamycin (ADM) and mitomycin (MMC) for 48 h. The induction of cell death was confirmed by microscopic analysis of cell morphology. Metabolic activity and the inhibitory rate (IR) of cells were evaluated by MTT assay. Expression of Bcl-2 was determined by immunohistochemistry of gastric cancer tissue samples. RESULTS: The IRs of cancer cells exposed to different chemotherapeutic drugs varied as follows: the IRs for TAX, CDDP and 5-FU were significantly higher than those for ADM and MMC (P < 0.01). Poorly differentiated gastric cancer cells were more sensitive than well-differentiated cells (P = 0.021). The positive rate of Bcl-2 expression was 80%, and Bcl-2 expression was significantly associated with chemoresistance to 5-FU (r(s) = 0.265, P = 0.041), ADM (r(s) = 0.425, P = 0.001) and MMC (r(s) = 0.40, P = 0.002). Furthermore, Bcl-2 expression was strongly associated with lymph node metastasis in gastric cancer (P = 0.009). CONCLUSION: Overexpression of Bcl-2 may predict a loss of the efficacy of the chemotherapy drugs 5-FU, ADM and MMC in patients with gastric cancer.
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