Potentiation of the effect of gemcitabine by emodin in pancreatic cancer is associated with survivin inhibition.
Pancreatic cancer is one human malignancy which has chemoresistant behavior to gemcitabine treatment. In this study, we revealed that emodin, an active component from Chinese medicinal herbs, could enhance pancreatic cancer cells apoptosis induced by gemcitabine. Survivin, a member of the inhibitor of apoptosis gene family, is involved in control of cell division and inhibition of apoptosis and described as a beta-catenin/Tcf/Lef target gene. Western blot and PCR analysis showed that emodin suppressed survivin expression in a dose- and time-dependent manner. We further demonstrated survivin expression could be up-regulated by gemcitabine. Surprisingly, survivin expression induced by gemcitabine could be inhibited in combination with emodin treatment. Moreover, cells treated with gemcitabine and emodin showed a preferential peri-plasmamembrane position of beta-catenin, blocking the translocation of beta-catenin to nucleus induced by gemcitabine. In addition to these in vitro results, we also found that emodin potentiates the antitumor effects of gemcitabine in vivo by down-regulating the expression of survivin and beta-catenin. Taken together, these results suggest that emodin potentiates gemcitabine antitumor activity through suppression of survivin gene in pancreatic cancer.
Guo
Qingqu
Q
Department of Surgery, The Second Affiliated Hospital, Zhejiang University College of Medicine, Cancer Institute of Zhejiang University, #88 Jiefang Road, Hangzhou City, 310009, PR China.
Chen
Ying
Y
Zhang
Bo
B
Kang
Muxing
M
Xie
Qiuping
Q
Wu
Yulian
Y
D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000627:therapeutic use*; D053148:Caspase 3 / Q000378:metabolism; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D017931:DNA Primers; D003841:Deoxycytidine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D004357:Drug Synergism; D004642:Emodin / Q000627:therapeutic use*; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins; D008869:Microtubule-Associated Proteins / Q000235:genetics*; D018482:Muscle, Skeletal / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000473:pathology; D051381:Rats; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013489:Suppression, Genetic; D000077022:Survivin; D000093542:Gemcitabine
D000964:Antimetabolites, Antineoplastic; C107489:BIRC5 protein, human; D017931:DNA Primers; D051034:Inhibitor of Apoptosis Proteins; D008869:Microtubule-Associated Proteins; D000077022:Survivin; D003841:Deoxycytidine; D053148:Caspase 3; D004642:Emodin; D000093542:Gemcitabine