Oleanolic acid inhibits colorectal cancer angiogenesis in vivo and in vitro via suppression of STAT3 and Hedgehog pathways.
Angiogenesis is an essential process of cancer progression and is regulated by multiple intracellular signaling pathways, including signal transducer and activator of transcription 3 (STAT3) and sonic hedgehog (SHH). Thus, these pathways have become a promising target for anti‑cancer therapeutic strategies. Oleanolic acid (OA) is an active compound present in various herbal medicines, which have been used historically for the clinical treatment of various types of human malignancies, including colorectal cancer (CRC). The present study used a CRC mouse xenograft model and human umbilical vein endothelial cells (HUVECs) to evaluate the effect of OA on tumor angiogenesis and on the activation of the STAT3 and SHH signaling pathways. It was determined that OA treatment significantly inhibited tumor growth and reduced intratumoral microvessel density (MVD) in CRC mice. In addition, OA treatment inhibited the proliferation, migration and tube formation in HUVECs, in a dose and time-dependent manner. Furthermore, OA markedly suppressed the activation of the STAT3 and SHH signaling pathways and inhibited the expression of the pro‑angiogenic vascular endothelial growth factor A and basic fibroblast growth factor, two important target genes of the aforementioned signaling pathways. Therefore it is suggested that inhibition of tumor angiogenesis via the suppression of multiple signaling pathways may be one of the underlying mechanisms by which OA exerts its anti-cancer effect.
Department of Disease Prevention and Healthcare, Fujian Provincial Hospital, Fuzhou, Fujian 350001, P.R. China.
Li
L
Li
Academy of Integrative Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian 350122, P.R. China.
Jiumao
J
Lin
Hangzhou Naval Sanatorium of Nanjing Military Area Command, Hangzhou, Zhejiang 310002, P.R. China.
Guodong
G
Sun
Academy of Integrative Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian 350122, P.R. China.
Lihui
L
Wei
Academy of Integrative Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian 350122, P.R. China.
Aling
A
Shen
Hangzhou Naval Sanatorium of Nanjing Military Area Command, Hangzhou, Zhejiang 310002, P.R. China.
Mingyue
M
Zhang
Academy of Integrative Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian 350122, P.R. China.
Jun
J
Peng
D000818:Animals; D045744:Cell Line, Tumor; D015179:Colorectal Neoplasms / Q000737:chemistry* / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D053823:Hedgehog Proteins / Q000096:biosynthesis*; D006801:Humans; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009363:Neoplasm Proteins / Q000096:biosynthesis*; D009389:Neovascularization, Pathologic / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D009828:Oleanolic Acid / Q000494:pharmacology*; D050796:STAT3 Transcription Factor / Q000096:biosynthesis*; D015398:Signal Transduction / Q000187:drug effects*
D053823:Hedgehog Proteins; D009363:Neoplasm Proteins; C509239:SHH protein, human; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D009828:Oleanolic Acid