STUDY ON INVASION AND METASTASIS OF HEPATOCELLULAR CARCINOMA BY MST BASED ON MAPK-ERK SIGNALING PATHWAY

Yong Meng¹, Lihong He^{2, 3}, Xiuyong Sun^{4, *}

Department of Hepatobiliary Surgery, The First Affiliated Hospital of Shantou University Medical College, Shantou, Guangdong 515041 China - ²First Clinical Medical College of Lanzhou University, Lanzhou, PR China - ³The First Hospital of Lanzhou University, Lanzhou, PR China - ⁴Department of Hepatobiliary Surgery, the Third People's Hospital of Qingdao, Qingdao, PR China

Objective: To analyse the mechanism of invasion and metastasis of hepatocellular carcinoma by MST based on the MAPK-ERK signalling pathway. 

Methods: Human hepatoma cell lines were cultured in vitro and cells that were grown in logarithm were divided into a control group (8 cells, no treatment), a high expression group (8 cells, treatment with high expression of MST4 transfection), and a low expression group (8 cells, treatment with low expression of MST4 transfection). Real-time quantitative PCR was used to detect the expression of the inflammatory factors present in each group of hepatoma cells; MTT assay was used to detect the proliferation of cells in each group; Transwell assay was used to detect the invasion and migration ability of each group; Western blot was used to detect the expression of ERK, p-ERK protein; and ELISA was used to detect changes in the inflammatory factor levels in each group of rats. 

Results: The real-time quantitative PCR results showed that the transcription levels of IL-6, IL-1β, TNF-α, and CCL-2 in high expression group of MST4 cells were significantly higher than those in the control group and the low expression group, and the difference was statistically significant (P<0.01); the MTT assay showed that the absorbance of hepatocarcinoma cells in the high expression group was also found to be significantly higher than both the control group and the low expression group, with the difference being statistically significant (P<0.01). Transwell test results showed that the number of invasion and migration of hepatocarcinoma cells in the high expression group was also significantly higher than that of the control group and the low expression group, with the difference being statistically significant (P<0.01). The results of the Western blot showed that there was no significant difference in the expression of ERK protein between the three groups (P>0.05). Furthermore, it was found that the expression of p-ERK protein in the high expression group of MST4 was significantly higher than that of the control group and low expression group, and the difference was statistically significant (P<0.01). The secretion of IL-6, IL-1β, TNF-α, CCL-2 of liver cancer cells in high expression group was also significantly higher than that of the control group and the ERK inhibitor group (P<0.01), which indicated that ERK inhibitors can significantly inhibit the secretion of inflammatory factors by liver cancer cells. 

Conclusion: MST4 can promote tumour secretion of inflammatory factors and enhance the invasion and metastasis ability of liver cancer cells through a MAPK-ERK signalling pathway.