Abstract
BackgroundRecepteur d’origine nantais (RON) is a receptor tyrosine kinase whose overexpression has been observed in human gastric cancers. This study aimed to determine whether overexpression of the variant RONΔ160 could induce tumorigenicity of gastric cancer cells in vitro or in vivo, and whether its specific small molecule inhibitor (Compound I) could inhibit the effect of RONΔ160.MethodsWe constructed human gastric cancer cell line MGC-803 that was stably transfected with a recombinant plasmid expressing RONΔ160, and the effect of RONΔ160 overexpression and macrophage-stimulating protein (MSP) activation on proliferation, migration and invasion abilities of MGC-803 cells were evaluated. Tumor-bearing mice with gastric cancer cells were used to analyze the effects of RONΔ160 overexpression and Compound I on implanted tumor growth.ResultsIn vitro, overexpression of RONΔ160 in MGC-803 cells resulted changes to their cell morphology, and promoted cell proliferation, migration and invasion. In addition, overexpression of RONΔ160 increased the proportion of cells in the S phase. The effect of RONΔ160 was significantly enhanced by induction of MSP inducing (p < 0.05). In vivo, RONΔ160 promoted the growth of MGC-803 cells in nude mice, including increased tumor size and weight, and lower tumor incubation period. The Compound I inhibited the tumorigenic abilities of RONΔ160 (p <0.05).ConclusionsThe results indicate that overexpression of the variant RONΔ160 altered the phenotype and tumorigenicity of MGC-803 cells. Its specific small molecule inhibitor could inhibit the effect of RONΔ160. Therefore, the variant RONΔ160 may become a potential therapeutic target for gastric cancer.
Highlights
Recepteur d’origine nantais (RON) is a receptor tyrosine kinase whose overexpression has been observed in human gastric cancers
RONΔ160 improves the proliferation of MGC-803 cells Cell proliferation was measured with the Cell counting kit 8 (CCK-8) cell proliferation assay
The results showed that the overexpression of RONΔ160 promoted significant proliferation of MGC-803 cells in the RONΔ160 group compared with the MGC-803 and empty vector control (p < 0.05)
Summary
Recepteur d’origine nantais (RON) is a receptor tyrosine kinase whose overexpression has been observed in human gastric cancers. This study aimed to determine whether overexpression of the variant RONΔ160 could induce tumorigenicity of gastric cancer cells in vitro or in vivo, and whether its specific small molecule inhibitor (Compound I) could inhibit the effect of RONΔ160. Studies have shown that the abnormal expression of RON, a member of the large RTK protein family, plays an important role in the incidence and development of tumors [1]. RON plays an important role in the growth, Zhou et al Cancer Cell International (2015) 15:9 the binding of the 53 kDa α chain with the 30 kDa β chain through disulfide bonds. RON contains functional domains that play important roles in ligand binding, protein maturation and bioactivity [5,10]. The effect of RONΔ160 on the incidence and development of gastric cancer has not been reported
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