Inhibitory effect and mechanism of exogenous mammalian sterile 20-like kinase 1 on the growth of human colorectal cancer

The present study aimed to observe the inhibitory effect and preliminary mechanism of exogenous mammalian sterile 20-like kinase 1 (MST1) on the growth of colorectal cancer SW480 cells. The SW480 cells were randomly divided into the following groups: Control, empty enhanced green fluorescent protein (EGFP) plasmid (pEGFP-N1), MST1 EGFP plasmid (pEGFP-MST1), 20 µmol/l fluorouracil (5-FU) and pEGFP-MST1 + 5-FU. An MTS colorimetric assay was used to detect cell viability, Hoechst 33342 staining was used to observe cell apoptosis, and western blotting and immunohistochemistry were used to detect the levels of the proteins MST1, yes-associated protein (YAP), phospho-YAP1 (Ser127), p53 and p53 upregulated modulator of apoptosis (PUMA). In addition, nude mice were injected with SW480 cells to assess the tumor inhibition rates. Compared with the control group, the growth inhibition and apoptosis rates, the levels of MST1, p53 and PUMA, and the ratios of phospho-YAP1/YAP in the pEGFP-MST1 and pEGFP-MST1 + 5-FU groups were increased significantly (P<0.01). Additionally, relative to the control group, the tumor inhibition rates in the nude mice transplanted with SW480 cells of the pEGFP-MST1 and pEGFP-MST1 + 5-FU groups were 48.52±1.63 and 87.28±2.58%, respectively, and the positive rates of phospho-YAP1 (Ser127) protein in nuclei increased significantly (P<0.01). Overall, exogenous MST1 effectively inhibited the proliferation and growth of transplanted human colorectal cancer cells and promoted cancer cell apoptosis. The mechanism involved may be associated with the increase of intracellular phospho-YAP1 (Ser127) protein.