[Reversal of chemoresistance to vincristine in gastric cancer cells by NF-kappaB inhibitor].
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.


CONCLUSIONS
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.
Wang
Wei
W
Department of Gastroenterology, Renmin Hospital of Wuhan University, Wuhan 430060, China.
Luo
He-sheng
HS
D000230:Adenocarcinoma / Q000473:pathology; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology; D045744:Cell Line, Tumor; D019008:Drug Resistance, Neoplasm / Q000187:drug effects*; D006801:Humans; D007976:Leupeptins / Q000494:pharmacology*; D016328:NF-kappa B / Q000037:antagonists & inhibitors*; D013274:Stomach Neoplasms / Q000473:pathology*; D014750:Vincristine / Q000494:pharmacology*
D000972:Antineoplastic Agents, Phytogenic; D007976:Leupeptins; D016328:NF-kappa B; D014750:Vincristine; C072553:benzyloxycarbonylleucyl-leucyl-leucine aldehyde