Enhanced anti-tumor effect of combination therapy with gemcitabine and apigenin in pancreatic cancer.
Apigenin is a dietary flavonoid possessing therapeutic potential against cancers. This study was designed to investigate whether combination therapy with gemcitabine and apigenin enhanced anti-tumor efficacy in pancreatic cancer. In vitro, the combination treatment resulted in more growth inhibition and apoptosis through the down-regulation of NF-kappa B activity with suppression of Akt activation in pancreatic cancer cell lines (MiaPaca-2, AsPC-1). In vivo, the combination therapy augmented tumor growth inhibition through the down-regulation of NF-kappa B activity with the suppression of Akt in tumor tissue. The combination of gemcitabine and apigenin enhanced anti-tumor efficacy through Akt and NF-kappa B activity suppression and apoptosis induction.
Lee
Sang Hyub
SH
Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, 110-744, Yeongeon-dong 28, Jongno-gu, Seoul, Republic of Korea.
Ryu
Ji Kon
JK
Lee
Kyeung-Yeup
KY
Woo
Sang Myung
SM
Park
Joo Kyung
JK
Yoo
Ji Won
JW
Kim
Yong-Tae
YT
Yoon
Yong Bum
YB
D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology* / Q000627:therapeutic use; D047310:Apigenin / Q000008:administration & dosage; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation; D004357:Drug Synergism; D006801:Humans; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D023041:Xenograft Model Antitumor Assays; D051028:bcl-2-Associated X Protein / Q000378:metabolism; D000093542:Gemcitabine
D000964:Antimetabolites, Antineoplastic; C494826:BAX protein, human; D016328:NF-kappa B; D051028:bcl-2-Associated X Protein; D003841:Deoxycytidine; D047310:Apigenin; D051057:Proto-Oncogene Proteins c-akt; D000093542:Gemcitabine