title: Curcumin reverses chemoresistance of human gastric cancer cells by downregulating the NF-κB transcription factor.
abstract: Gastric cancer remains one of the major health problems worldwide. Chemotherapy is an important therapeutic modality for gastric cancer, but the success rate of this treatment is limited because of chemoresistance. The ubiquitously expressed transcription factor NF-κB has been suggested to be associated with chemoresistance of gastric cancer. Agents that can either enhance the effects of chemotherapeutics or overcome chemoresistance to chemotherapeutics are needed for the treatment of gastric cancer. Curcumin, a component of turmeric, is one such agent that has been shown to suppress NF-κB and increase the efficacy of chemotherapy. In this study, we investigated whether curcumin can reverse chemoresistance by downregulating NF-κB in human gastric cancer cells. SGC-7901 human gastric cancer cells was treated with chemotherapeutics (etoposide and doxorubicin) or by combined application of curcumin and chemotherapeutics. The viability of SGC-7901 cells was measured by MTT assay. Apoptosis of SGC-7901 cells was detected using the TUNEL and Annexin V/PI methods. The protein levels of NF-κB were analyzed by immunocytochemical staining. EMSA was used to confirm the increased nuclear translocation of RelA. The protein levels of p-IκBα, Bcl-2 and Bcl-xL were analyzed by Western blotting. The chemotherapeutics (etoposide and doxorubicin) suppressed the growth of SGC-7901 cells, in a time-dose-dependent manner. Use of curcumin in addition to these agents can suppress cell growth further (inhibitory rate: doxorubicin vs. doxorubicin + curcumin, 33% vs. 45%, p<0.05; etoposide vs. etoposide + curcumin, 35% vs. 48%, p<0.05). Furthermore, chemotherapeutics induced apoptosis of SGC-7901 cells and activated NF-κB. The combination of curcumin and chemotherapeutics induced apoptosis of SGC-7901 cells further, attenuated the activation of NF-κB, and reduced expression of the NF-κB-regulated anti-apoptotic gene products Bcl-2 and Bcl-xL. Curcumin potentiates the antitumor effects of chemotherapeutics in gastric cancer by suppressing NF-κB and NF-κB-regulated anti-apoptotic genes.
authors.affiliation: Department of Gastro-enterology, Sir Run Run Shaw Affiliated Hospital of Zhejiang University, 3 East Qingchun Road, Hangzhou 310016, Zhejiang, PR China. yuliangliang@sina.com.cn
authors.forename: Liang-Liang
authors.initials: LL
authors.lastname: Yu
authors.forename: Jia-Guo
authors.initials: JG
authors.lastname: Wu
authors.forename: Ning
authors.initials: N
authors.lastname: Dai
authors.forename: Hong-Gang
authors.initials: HG
authors.lastname: Yu
authors.forename: Jian-Min
authors.initials: JM
authors.lastname: Si
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D048708:Cell Growth Processes / Q000187:drug effects; D045744:Cell Line, Tumor; D003474:Curcumin / Q000008:administration & dosage / Q000494:pharmacology*; D004273:DNA, Neoplasm / Q000378:metabolism; D015536:Down-Regulation / Q000187:drug effects; D004317:Doxorubicin / Q000008:administration & dosage / Q000494:pharmacology; D019008:Drug Resistance, Neoplasm; D004357:Drug Synergism; D005047:Etoposide / Q000008:administration & dosage / Q000494:pharmacology; D006801:Humans; D020672:I-kappa B Proteins / Q000378:metabolism; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D051996:Transcription Factor RelA / Q000096:biosynthesis / Q000235:genetics; D051020:bcl-X Protein / Q000378:metabolism
chemical_list: D004273:DNA, Neoplasm; D020672:I-kappa B Proteins; D016328:NF-kappa B; C000606204:NFKBIA protein, human; D019253:Proto-Oncogene Proteins c-bcl-2; D051996:Transcription Factor RelA; D051020:bcl-X Protein; D000072000:NF-KappaB Inhibitor alpha; D005047:Etoposide; D004317:Doxorubicin; D003474:Curcumin