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Mechanism of Jianpi Huayu Decoction Enhancing Dormancy of Liver Cancer by Inhibiting Angiogenesis
Authors:  Ju-Ze Lin, M.D., Yong-Xin Lin, M.M., Chang-Jun Wang, M.D., Le Su, M.M., Qiao Su, M.M., Xu-Hui Huang, M.M., Wei Tan, M.D., and Li-Zhu Lin, M.D.
  Objective: To study the anti-hepatoma effect of Jianpi Huayu decoction (JHD) by studying the mechanism of anti-angiogenesis inhibition by JHD by using modern medical research methods. This study is helpful to search for drugs that can induce tumor dormancy of liver cancer and prevent recurrence after operation.
Study Design:
A mouse liver cancer dormancy model was constructed. The dormancy was broken by truncating the mouse tail, and then those mice were administered JHD at dosages of 24.96 g/kg, 12.48 g/kg, and 6.24 g/kg. The tumor dormancy rate was detected at 1, 4, 8, and 15 days after JHD administration.
JHD significantly increased the dormancy rate of hepatocellular carcinoma (HCC) (p=0.01). Moreover, higher doses induced a higher dormancy rate. That is, JHD, with the dose of 24.96 g/kg, can significantly increase the dormancy rate of HCC at 75% (p<0.01), which was about 3 times as high as that in the control group. HE staining, quantitative polymerase chain reaction (QPCR), and western blot were used to detect the positive expression of HIF-1α, VEGF, MMP-9, TIMP-1, and EMMPRIN proteins and RNA, respectively. The results show that JHD significantly decreases the protein and RNA expression of HIF-1α, VEGF, MMP-9, TIMP-1, and EMMPRIN and that the rate of decrease is related to the dosage of JHD. Finally, flow cytometry was used to detect the proliferation of circulating endothelial cells (CECs) and viable CECs (vCECs) in peripheral blood. The results show that JHD inhibits the proliferation of CECs and vCECs, and the number of cells decreases with the increase of JHD dose.
JHD may enhance the dormancy of HCC by inhibiting angiogenesis, and the mechanism may be achieved by affecting the expression of HIF-1α, VEGF, MMP-9, TIMP-1, and EMMPRIN genes and proteins. In addition, the dose of JHD is closely related to its function.
Keywords:  angiogenesis; drugs, Chinese herbal; endothelial cells; flow cytometry; hepatocellular carcinoma; Jianpi Huayu; liver cancer; phytotherapy; renal insufficiency, chronic; tumor dormancy
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