title: Emodin potentiates the antitumor effects of gemcitabine in PANC-1 pancreatic             cancer xenograft model in vivo via inhibition of inhibitors of apoptosis.
abstract: Pancreatic cancer is a highly aggressive malignant disease. Gemcitabine             is currently the standard first-line chemotherapeutic agent for pancreatic cancer.             As members of apoptosis inhibitors, Survivin and XIAP play an important role in             chemotherapy resistance in pancreatic cancer. Emodin has therapeutic potential             against cancers. This study was designed to investigate whether combination therapy             with gemcitabine and emodin enhanced antitumor efficacy in pancreatic cancer.             The application of the combination therapy triggered significantly higher frequency             of pancreatic cancer cell apoptosis. Our research demonstrated that the combination             of emodin and gemcitabine resulted in significantly reduced tumor volumes compared             to gemcitabine or emodin treatment alone. Immunohistochemistry and western immunoblot             analyses showed that Survivin and XIAP expression were downregulated in emodin             and the combination groups compared to the other two groups. Reverse transcriptase             polymerase chain reaction analyses showed that Survivin and XIAP mRNA expression             in emodin and the combination groups were downregulated significantly compared             to the other two groups. Furthermore, the expression of the nuclear transcription             factor κB (NF-κB) protein and NF-κB mRNA were downregulated in the emodin and             the combination groups. DNA-binding activity of NF-κB was inhibited in emodin             and combination groups compared to the other groups. This study suggests that             emodin potentiates the antitumor effects of gemcitabine in PANC-1 cell xenografts             via promotion of apoptosis and IAP suppression.
authors.affiliation: Department of Hepatobiliary-Pancreatic Surgery, The Second Affiliated                     Hospital of Wenzhou Medical College, Wenzhou, P.R. China.
authors.forename: Hong-Chun
authors.initials: HC
authors.lastname: Guo
authors.forename: He-Qi
authors.initials: HQ
authors.lastname: Bu
authors.forename: Jiang
authors.initials: J
authors.lastname: Luo
authors.forename: Wei-Tian
authors.initials: WT
authors.lastname: Wei
authors.forename: Dian-Lei
authors.initials: DL
authors.lastname: Liu
authors.forename: Hui
authors.initials: H
authors.lastname: Chen
authors.forename: Hong-Fei
authors.initials: HF
authors.lastname: Tong
authors.forename: Zhao-Hong
authors.initials: ZH
authors.lastname: Wang
authors.forename: Hua-Yong
authors.initials: HY
authors.lastname: Wu
authors.forename: Hong-Hai
authors.initials: HH
authors.lastname: Li
authors.forename: Ming-Ming
authors.initials: MM
authors.lastname: Zuo
authors.forename: Wei
authors.initials: W
authors.lastname: Li
authors.forename: Sheng-Zhang
authors.initials: SZ
authors.lastname: Lin
mesh_terms: D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology* / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects*; D051017:Apoptosis Regulatory Proteins / Q000037:antagonists & inhibitors*; D020169:Caspases / Q000378:metabolism; D045744:Cell Line, Tumor; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D015536:Down-Regulation; D004357:Drug Synergism; D004642:Emodin / Q000008:administration & dosage; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins / Q000235:genetics / Q000378:metabolism; D019394:Ki-67 Antigen / Q000378:metabolism; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000378:metabolism; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000473:pathology; D000077022:Survivin; D047368:Tumor Burden / Q000187:drug effects; D051636:X-Linked Inhibitor of Apoptosis Protein / Q000235:genetics / Q000378:metabolism; D023041:Xenograft Model Antitumor Assays; D000093542:Gemcitabine
chemical_list: D051017:Apoptosis Regulatory Proteins; C107489:BIRC5 protein, human; D051034:Inhibitor of Apoptosis Proteins; D019394:Ki-67 Antigen; D016328:NF-kappa B; D000077022:Survivin; D051636:X-Linked Inhibitor of Apoptosis Protein; C496866:XIAP protein, human; D003841:Deoxycytidine; D020169:Caspases; D004642:Emodin; D000093542:Gemcitabine