title: Comparison of the effect of p65 siRNA and curcumin in promoting apoptosis             in esophageal squamous cell carcinoma cells and in nude mice.
abstract: The activation of the NF-κB signaling pathway plays a critical role in carcinogenesis. The role of the NF-κB pathway in esophageal squamous cell carcinoma (ESCC) remains ill-defined. The objective was to detect whether p65siRNA and curcumin could promote ESCC cell apoptosis and increase the sensitivity of ESCC cells to chemotherapeutic drugs by inhibiting the NF-κB signaling pathway, and to compared these two treatments. In the present study, the status of the NF-κB pathway, in the two ESCC cell lines Eca109 and EC9706, was analyzed and the ability of p65 siRNA and curcumin alone or in combination with 5-FU to modulate this pathway in vitro and in vivo was investigated. The results showed that the NF-κB signaling pathway in the ESCC cell lines was constitutively activated. Both p65 siRNA and curcumin mediated suppression of activation of the NF-κB signaling pathway via inhibition of the expression of p65 or IκBα phosphorylation in ESCC cell lines. The cells treated with combination of p65 siRNA or curcumin and 5-FU revealed a lower cell viability and higher apoptosis compared to those treated with 5-FU alone. In a human ESCC xenograft model, p65 siRNA or curcumin and 5-FU alone reduced the tumor volume, respectively, but their combination had the strongest anticancer effects. Curcumin was more effective than p65 siRNA in vitro and in vivo. Overall, our results indicate that the constitutively activated NF-κB signaling pathway plays a crucial role in these two ESCC cell lines and both p65siRNA and curcumin can promote ESCC cell apoptosis and enhance the sensitivity to 5-FU through suppression of the NF-κB signaling pathway. It is still a long time before RNA interference will be used in the clinic. Therefore, curcumin is proved to be useful in the treatment of ESCC as it is a pharmacologically safe compound without side effects.
authors.affiliation: Department of Pathophysiology, Basic Medical College, Zhengzhou University, Zhengzhou, Henan 450001, PR China.
authors.forename: Fang
authors.initials: F
authors.lastname: Tian
authors.forename: Caifeng
authors.initials: C
authors.lastname: Zhang
authors.forename: Weihong
authors.initials: W
authors.lastname: Tian
authors.forename: Yanan
authors.initials: Y
authors.lastname: Jiang
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Zhang
mesh_terms: D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology* / Q000627:therapeutic use; D017209:Apoptosis; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy / Q000235:genetics / Q000473:pathology*; D045744:Cell Line, Tumor; D048430:Cell Shape; D003474:Curcumin / Q000008:administration & dosage; D003593:Cytoplasm / Q000378:metabolism; D004938:Esophageal Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000473:pathology*; D005472:Fluorouracil / Q000008:administration & dosage; D055785:Gene Knockdown Techniques; D006801:Humans; D008297:Male; D051379:Mice; D008819:Mice, Nude; D016328:NF-kappa B / Q000378:metabolism; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics*; D015398:Signal Transduction; D051996:Transcription Factor RelA / Q000235:genetics* / Q000378:metabolism; D047368:Tumor Burden / Q000187:drug effects / Q000235:genetics; D023041:Xenograft Model Antitumor Assays
chemical_list: D016328:NF-kappa B; C498143:RELA protein, human; D034741:RNA, Small Interfering; D051996:Transcription Factor RelA; D003474:Curcumin; D005472:Fluorouracil