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  • Title: [Reversal of chemoresistance to vincristine in gastric cancer cells by NF-kappaB inhibitor].
    Author: Wang W, Luo HS.
    Journal: Zhonghua Zhong Liu Za Zhi; 2005 Jun; 27(6):335-8. PubMed ID: 16117894.
    Abstract:
    OBJECTIVE: To investigate the reversing effect of NF-kappaB inhibitor MG-132 on chemoresistance of gastric cancer cells to vincristine. METHODS: In vincristine-resistant human gastric cancer cells (SGC7901/VCR) and the parental sensitive clone (SGC7901), NF-kappaB-DNA binding activity was determined by electrophoreses mobility shift assay (EMSA). The inhibition level of kappaB (IkappaB-alpha) expression was measured by cellular-ELISA. Immunocytochemistry was used to detect the translocation of p65 and chemosensitivity of the cells was determined by MTT assay. RESULTS: Compared with the parental SGC7901 cells, both the baseline and VCR-induced NF-kappaB-DNA binding activities in various concentrations were all higher in the SGC7901/VCR cells. Pretreatment with MG-132, the NF-kappaB inhibitor, for 30 minutes remarkably reduced the NF-kappaB activation, IkappaB-alpha degradation and nuclear translocation of p65. As to the SGC7901/VCR cells and the parental sensitive SGC7901 cells, the IC(50) values for VCR were 40.03 mg/L and 0.26 mg/L, respectively. MG-132 (2.5 micromol/L) significantly enhanced the toxicity of VCR in SGC7901/VCR cells and decreased the resistance index from 154.0 to 16.5. However, MG-132 did not show an obvious effect on the VCR sensitivity in sensitive SGC7901 cells. CONCLUSION: Our data indicate that inhibition of NF-kappaB activation in gastric cancer cells may reverse the drug resistance to VCR in the cancer cells and increase the efficiency of chemotherapy.
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