Yi Ai Fang, a traditional Chinese herbal formula, impacts the vasculogenic mimicry formation of human colorectal cancer through HIF-1α and epithelial mesenchymal transition.
BACKGROUND
Yi Ai Fang (YAF), a traditional Chinese medicine (TCM) formula, has been identified to have anticancer activity in our previously studies. The present study aimed to explore the potential mechanism of YAF suppression of VM on colorectal cancer (CRC) in vitro and in vivo.


METHODS
Cell viability was measured by CCK-8 assay. HIF-1α, E-cd(E-cadherin), Claudin-4, and VIM (Vimentin) expressions level in vitro were evaluated by Western blot or RT-PCR. In addition, Human CRC HCT-116 cells were implanted in BALB/c nude mice; mice with xenografted tumors were randomly administrated vehicle (control), 8, 16, or 32 mg/mL YAF, or 1 mg/mL fluorouracil (5-FU). HIF-1α, E-cd, Claudin-4, and VIM expression in these tumors were determined by IHC.


RESULTS
YAF effectively inhibited the growth and the formation of vasculogenic mimicry (VM) of CRC cells in a dose-dependent trend. YAF restrained the formation of vasculogenic mimicry(VM) through HIF-1α/EMT pathway in CRC. YAF suppressed VM was triggered by activation of E-cd and Claudin-4,which are characteristics of endothelial cells,and inhibition of HIF-1α and VIM in vitro. In vivo data showed that YAF remarkably inhibited growth of the xenografted tumors. The YAF-treated tumor samples were analyzed by IHC for levels of HIF-1α/EMT related proteins HIF-1α, E-cd, Claudin-4, and VIM. The results indicated that YAF significantly enhanced expression of E-cd and Claudin-4,but decreased expression of HIF-1α, VIM in a dose-dependent manner.


CONCLUSIONS
In conclusion, this study provided the first direct evidence that YAF inhibited the formation of VM in human CRC, suggesting that YAF may be considered as a useful target for cancer therapy.
Oncology Department of Shanghai Municipal Hospital of Traditional Chinese Medicine affiliated to Shanghai TCM University, Shanghai, 200071, China.
Fenggang
F
Hou
Oncology Department of Shanghai Municipal Hospital of Traditional Chinese Medicine affiliated to Shanghai TCM University, Shanghai, 200071, China.
Wen
W
Li
Oncology Department of Shanghai Municipal Hospital of Traditional Chinese Medicine affiliated to Shanghai TCM University, Shanghai, 200071, China.
Qi
Q
Shi
Oncology Department of Shanghai Municipal Hospital of Traditional Chinese Medicine affiliated to Shanghai TCM University, Shanghai, 200071, China.
Hongjia
H
Li
Oncology Department of Shanghai Municipal Hospital of Traditional Chinese Medicine affiliated to Shanghai TCM University, Shanghai, 200071, China.
Shanshan
S
Liu
Oncology Department of Shanghai Municipal Hospital of Traditional Chinese Medicine affiliated to Shanghai TCM University, Shanghai, 200071, China.
Shaoqi
S
Zong
Oncology Department of Shanghai Municipal Hospital of Traditional Chinese Medicine affiliated to Shanghai TCM University, Shanghai, 200071, China.
Jianlin
J
Ren
Department of Gastrointestinal Surgery, Shandong University Affiliated Shandong Cancer Hospital and Institute, 117 Jiyan Road, Jinan, Shandong, 250000, China. 13917367207@163.com.
Jie
J
Chai
Mental diseases of Shanghai Municipal Hospital of Traditional Chinese Medicine affiliated to Shanghai TCM University, 274 Zhijiang Road, Shanghai, 200071, China. xujianszy@163.com.
Jian
J
Xu
D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D015179:Colorectal Neoplasms / Q000378:metabolism*; D004365:Drugs, Chinese Herbal / Q000494:pharmacology*; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects*; D045325:HCT116 Cells; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism*; D051379:Mice; D008819:Mice, Nude; D009389:Neovascularization, Pathologic / Q000473:pathology; D023041:Xenograft Model Antitumor Assays
D004365:Drugs, Chinese Herbal; D051795:Hypoxia-Inducible Factor 1, alpha Subunit
Colorectal cancer; EMT; HIF-1α; Vasculogenic mimicry; Yi Ai Fang