title: Expression analysis of Cdc42 in lung cancer and modulation of its expression             by curcumin in lung cancer cell lines.
abstract: Cdc42, a Rho GTPase family member, is involved in cell transformation, proliferation,             survival, invasion and metastasis of human cancer cells. Overexpression of Cdc42             has been reported in several types of human cancer. However, the underlying mechanisms             are not well understood. The present study showed that Cdc42 was overexpressed             in 80 of 110 primary lung cancer patients, and overexpression of Cdc42 was significantly             associated with high TNM stage and lymph node metastasis. Moreover, RNAi-mediated             suppression of Cdc42 expression reduced actin ﬁlopodia formation, migration and             invasion potential of a highly metastatic lung cancer cell line, 801D. In parallel,             801D cells were treated with curcumin and the effect on the expression of the             Cdc42 gene at the transcriptional and translational levels was analyzed by RT-PCR             and Western blotting. Curcumin inhibited cell migration, invasion and downregulated             Cdc42 gene and Cdc42-related target gene expression in 801D cells. It also induced             rearrangements of the actin cytoskeleton. These effects mimicked those of Cdc42             knockdown. Furthermore, xenograft experiments confirmed the suppression of tumor             growth and invasion in vivo, which was due to the effect of curcumin and the inhibition             of Cdc42 by curcumin. Our results showing the downregulation of Cdc42 expression             by curcumin in lung cancer cells taken together with the clinical data suggest             a potential therapeutic role for curcumin in inducing Cdc42-mediated inhibition             of invasion of lung cancer cells.
authors.affiliation: Department of Respiratory Disease, The 117th Hospital of PLA, Hang Zhou 310013, PR China.
authors.forename: Qing-Yong
authors.initials: QY
authors.lastname: Chen
authors.forename: De-Min
authors.initials: DM
authors.lastname: Jiao
authors.forename: Qing-Hua
authors.initials: QH
authors.lastname: Yao
authors.forename: Jie
authors.initials: J
authors.lastname: Yan
authors.forename: Jia
authors.initials: J
authors.lastname: Song
authors.forename: Fang-Yuan
authors.initials: FY
authors.lastname: Chen
authors.forename: Guo-Hua
authors.initials: GH
authors.lastname: Lu
authors.forename: Jian-Ying
authors.initials: JY
authors.lastname: Zhou
mesh_terms: D008841:Actin Cytoskeleton / Q000187:drug effects / Q000378:metabolism; D000704:Analysis of Variance; D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D015153:Blotting, Western; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D016009:Chi-Square Distribution; D003474:Curcumin / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005260:Female; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000235:genetics / Q000401:mortality / Q000473:pathology; D008207:Lymphatic Metastasis; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D016133:Polymerase Chain Reaction; D034622:RNA Interference; D012333:RNA, Messenger / Q000378:metabolism; D015533:Transcriptional Activation / Q000187:drug effects; D014162:Transfection; D047368:Tumor Burden / Q000187:drug effects; D023041:Xenograft Model Antitumor Assays; D020764:cdc42 GTP-Binding Protein / Q000235:genetics / Q000378:metabolism*
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D012333:RNA, Messenger; D020764:cdc42 GTP-Binding Protein; D003474:Curcumin