Liver Cancer
Sorafenib regulates vascular endothelial growth factor by runt-related transcription factor-3 to inhibit angiogenesis in hepatocellular carcinoma
Chai Mengyin, Kou Buxin, Fu Zhi, Wei Feili, Dou Shuangshuang, Chen Dexi, Liu Xiaoni
Published 2022-07-20
Cite as Chin J Hepatol, 2022, 30(7): 770-776. DOI: 10.3760/cma.j.cn501113-20201221-00670
Abstract
ObjectiveTo investigate the molecular mechanism of sorafenib against hepatocellular carcinoma.
MethodsSorafenib efficacy was screened and verified by the hepatocellular carcinoma patient-derived tumor xenograft (PDX) model. Veterinary B-mode ultrasonography and in vivo confocal laser scanning microscopy were used to observe PDX angiogenesis. Immunohistochemistry was used to observe the expression of proliferation and angiogenesis-related proteins in PDX tissue. Real-time quantitative PCR technology was used to observe the RUNX3 gene in PDX tissues. SPSS 17.0 statistical software was used for statistical analysis.
ResultsFour cases of PDX were used to screen the efficacy of sorafenib. PDX1 had a significant response to sorafenib, with an inhibition rate of 68.07%. Compared with the control group, sorafenib had significantly inhibited PDX1 relative tumor volume (5.76±2.14 vs. 11.71±2.87, P<0.05). Cell division index (39.50±7.72 vs. 67.10±9.14, P<0.05) and Ki67 expression (288.6±43.40 vs. 531.70±55.60, P<0.05) were significantly decreased. Veterinary B-mode ultrasonography showed evident blood flow signals in PDX1 tumors. In vivo confocal laser scanning microscopy results showed that sorafenib had significantly reduced the total vessel length (1573.00±236.21 vs. 2675.03±162.00, P<0.05) and area (11 145.33±1931.97 vs. 20 105.37±885.93, P<0.05)) of PDX1 tumors. Immunohistochemical results showed that sorafenib had significantly down-regulated the protein expressions of CD34 (27.55±3.76 vs. 45.47±5.57, P<0.05), VEGF (16.33±2.86 vs. 22.77±3.20, P<0.05) and MVD (38.75±6.01 vs. 55.50±8.61, P<0.05). Real-time PCR results showed that sorafenib had significantly up-regulated RUNX3 gene expression (2.14±0.71 vs. 1.00±0.36, P<0.05). However, there was a negative correlation between the expression of RUNX3 gene and the ratio of VEGF-positive cells in sorafenib group (R2=0.509 7).
ConclusionSorafenib may inhibit the PDX angiogenesis and the growth of hepatocellular carcinoma by regulating the RUNX3-VEGF pathway.
Key words:
Sorafenib; Liver cancer; Angiogenesis; Runt related transcription factor 3; Patient-derived xenograft
Contributor Information
Chai Mengyin
Beijing You'an Hospital,Capital Medical University, Beijing 100069, China
Beijing Institute of Hepatology, Beijing 100069, China
Kou Buxin
Beijing You'an Hospital,Capital Medical University, Beijing 100069, China
Beijing Institute of Hepatology, Beijing 100069, China
Fu Zhi
Beijing You'an Hospital,Capital Medical University, Beijing 100069, China
Wei Feili
Beijing You'an Hospital,Capital Medical University, Beijing 100069, China
Beijing Institute of Hepatology, Beijing 100069, China
Dou Shuangshuang
Beijing You'an Hospital,Capital Medical University, Beijing 100069, China
Beijing Institute of Hepatology, Beijing 100069, China
Chen Dexi
Beijing You'an Hospital,Capital Medical University, Beijing 100069, China
Beijing Institute of Hepatology, Beijing 100069, China
Liu Xiaoni
Beijing You'an Hospital,Capital Medical University, Beijing 100069, China
Beijing Institute of Hepatology, Beijing 100069, China
