title: Paclitaxel-sensitization enhanced by curcumin involves down-regulation of nuclear factor-κB and Lin28 in Hep3B cells.
abstract: Although paclitaxel is an effective chemotherapeutic drug used in the treatment of many tumors, hepatoma cells, in particular, are known to be highly resistant to it. Previously, we discovered that Lin28 was closely associated with resistance to paclitaxel in Hep3B cells. The nuclear factor-kappa B (NF-κB) transcription factor, which plays an important role in tumor survival, directly activates Lin28 expression through a binding site on the first intron. Curcumin, a non-toxic anti-inflammatory agent, inhibits NF-κB activity in vitro. In this study, we reported that a combination of curcumin and paclitaxel exhibited synergistic anti-proliferative and pro-apoptosis effects on Hep3B cells, and curcumin down-regulated paclitaxel-induced enhanced expression of Lin28 and NF-κB activation. Furthermore, our results revealed that curcumin reduced Lin28 levels via mechanisms directly mediated by inhibition of NF-κB activity. These mechanism-based observations evidence that curcumin enhances the sensitivity of hepatoma cells to paclitaxe, and strongly support the notion that paclitaxel in combination with curcumin may provide a superior therapeutic index for HCC chemotherapy.
authors.affiliation: a College of Life Science, Zhejiang Chinese Medical University , Zhejiang , China and.
authors.forename: Mingjie
authors.initials: M
authors.lastname: Zhou
authors.affiliation: b Department of neurosurgery , China-Japan Union Hospital, Jilin University , Jilin , China.
authors.forename: Zhaohui
authors.initials: Z
authors.lastname: Li
authors.affiliation: a College of Life Science, Zhejiang Chinese Medical University , Zhejiang , China and.
authors.forename: Ziwu
authors.initials: Z
authors.lastname: Han
authors.affiliation: a College of Life Science, Zhejiang Chinese Medical University , Zhejiang , China and.
authors.forename: Nan
authors.initials: N
authors.lastname: Tian
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D049109:Cell Proliferation / Q000187:drug effects; D003474:Curcumin / Q000008:administration & dosage; D019008:Drug Resistance, Neoplasm / Q000187:drug effects*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D006801:Humans; D008113:Liver Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism*; D017239:Paclitaxel / Q000008:administration & dosage; D012333:RNA, Messenger / Q000235:genetics; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014407:Tumor Cells, Cultured
chemical_list: C000715187:Lin28A protein, human; D016328:NF-kappa B; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D003474:Curcumin; D017239:Paclitaxel
keywords: Curcuma longa; Lin28; NF-κB; Taxus brevifolia; curcumin; hepatocellular carcinoma; paclitaxel