Combination treatment with artemisinin and oxaliplatin inhibits tumorigenesis in esophageal cancer EC109 cell through Wnt/ß-catenin signaling pathway.

BACKGROUND: Esophageal cancer (EC) is a prevalent malignant cancer worldwide. Interestingly, the antimalaria compound artemisinin (ART) is also reported to have anticancer potential, although its underlying mechanism in EC is unclear. In this study, we explored the anticancer role of ART in EC109 and further explored the combination of ART and oxaliplatin (OXA) for their synergetic anticancer functions. METHODS: Human EC cell line EC109 was used. After ART or oxaliplatin (OXA) treatment, cell proliferation, migration, and invasion were measured by MTT, transwell, and scratch wound assays, respectively. Flow cytometry was performed to examine the cell cycle and apoptosis. The mRNA and protein levels were determined using qRT-PCR and western blotting. RESULTS: The migration and invasion abilities of EC109 were suppressed by ART. This was due to the inhibitory effect of ART on the Wnt/ß-catenin signaling pathway. The levels of ß-catenin, c-myc, and survivin were also downregulated by ART. ART inhibits the proliferation of EC109 cells by arresting the cells in the G1-phase of cell cycle. By using LiCl, an activator of the Wnt/ß-catenin pathway, we further verified that the inhibition of the Wnt/ß-catenin pathway was indeed due to ART. Remarkably, ART enhanced the anticancer effects of OXA in EC109 cells. OXA combined with ART was found to be more efficient in decreasing tumor growth compared to the individual drugs. CONCLUSIONS: ART could suppress tumor progression by inhibiting Wnt/ß-catenin signaling pathway, and it may also enhance the antitumor effect of OXA in EC. Thus, ART could be a novel anticancer drug for EC treatment. KEY POINTS: SIGNIFICANT FINDINGS OF THE STUDY: ART could be a novel anticancer drug for esophageal cancer (EC) treatment. WHAT THIS STUDY ADDS: Combination treatment with artemisinin and oxaliplatin inhibits tumorigenesis in esophageal cancer EC109 cells through the Wnt/ß-catenin signaling pathway.

LINC00657/miR-26a-5p/CKS2 ceRNA network promotes the growth of esophageal cancer cells via the MDM2/p53/Bcl2/Bax pathway.

LncRNA LINC00657 has oncogenic or anti-carcinoma roles in different cancers, and yet its detailed molecular mechanism in esophageal cancer (EC) remains unclear. In addition, competitive endogenous RNA (ceRNA) regulatory lncRNA-miRNA-mRNA networks are critical for tumorigenesis and progression. Hence, the present study explored the roles of LINC00657 in EC and identified its relevant ceRNA network. We first detected the expression of LINC00657 in EC. Then, we applied starBase and TargetScan websites to find miR-26a-5p binding to LINC00657 and obtain CKS2 as a target of miR-26a-5p. The roles of LINC00657, miR-26a-5p or CKS2 in the proliferation, migration, invasion, and apoptosis of EC cells were respectively assessed by CCK-8, wound healing assay, transwell invasion assay, and flow cytometry. The changes of the MDM2/p53/Bcl2/Bax pathway were measured via Western blot. The results revealed that LINC00657 showed an aberrant high expression in EC cells, which promoted the growth of EC cells. Additionally, LINC00657 functioned as a sponge of miR-26a-5p, and LINC00657 negatively mediated miR-26a-5p to regulate the growth of EC cells. Furthermore, CKS2 was observed as a direct target of miR-26a-5p, and CKS2 controlled the growth of EC cells via the MDM2/p53/Bcl2/Bax pathway. Moreover, there was a positive correlation between LINC00657 and CKS2. LINC00657 knockdown inhibited CKS2 expression to suppress the proliferation, migration, and invasion of EC cells and induced apoptosis via regulating the MDM2/p53/Bcl2/Bax pathway. Collectively, LINC00657/miR-26a-5p/CKS2 ceRNA network could promote the progression of EC, which is good for understanding the molecular mechanism of EC and offers novel biomarkers for EC diagnosis and therapy.