Enhanced antitumor efficacy of gemcitabine by evodiamine on pancreatic cancer via regulating PI3K/Akt pathway.
Evodiamine has therapeutic potential against cancers. This study was designed to investigate whether combination therapy with gemcitabine and evodiamine enhanced antitumor efficacy in pancreatic cancer. In vitro application of the combination therapy triggered significantly higher frequency of pancreatic cancer cells apoptosis, inhibited the activities of PI3K, Akt, PKA, mTOR and PTEN, and decreased the activation of NF-κB and expression of NF-κB-regulated products. In vivo application of the combination therapy induced significant enhancement of tumor cell apoptosis, reductions in tumor volume, and inhibited activation of mTOR and PTEN. In conclusion, evodiamine can augment the therapeutic effect of gemcitabine in pancreatic cancer through direct or indirect negative regulation of the PI3K/Akt pathway.
Department of Oncological Surgery, Zhejiang Cancer Hospital, Hangzhou, China.
Wei-Tian
WT
Wei
Hui
H
Chen
Zhao-Hong
ZH
Wang
Zhong-Lin
ZL
Ni
Hai-Bin
HB
Liu
Hong-Fei
HF
Tong
Hong-Chun
HC
Guo
Dian-Lei
DL
Liu
Sheng-Zhang
SZ
Lin
D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D006801:Humans; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism; D051058:Oncogene Protein v-akt / Q000378:metabolism*; D010190:Pancreatic Neoplasms / Q000188:drug therapy*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D011799:Quinazolines / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D015398:Signal Transduction / Q000187:drug effects*; D000093542:Gemcitabine
D016328:NF-kappa B; D011799:Quinazolines; D003841:Deoxycytidine; C049639:evodiamine; D019869:Phosphatidylinositol 3-Kinases; D051058:Oncogene Protein v-akt; D000093542:Gemcitabine