Combination treatment with artemisinin and oxaliplatin inhibits tumorigenesis in esophageal cancer EC109 cell through Wnt/β‐catenin signaling pathway

Abstract

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/β‐catenin signaling pathway. The levels of β‐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/β‐catenin pathway, we further verified that the inhibition of the Wnt/β‐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/β‐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/β‐catenin signaling pathway.

TIP60 is required for tumorigenesis in non‐small cell lung cancer

“…We report that artemisinin treatment inhibited TIP60 expression and tumor progression. TIP60 regulates transcription of various genes, including NF‐κB , MYC , and CCND1 , 39–41 all also blocked by artemisinin and associated with antitumor activities of artemisinin, 42–44 suggesting that artemisinin exerts multiple anticancer effects via TIP60 regulation. However, artemisinin is not an ideal and specific compound for clinical suppression of TIP60 in part because high concentrations are required to inhibit TIP60 expression.…”

KIFC3 promotes proliferation, migration and invasion of esophageal squamous cell carcinoma cells by activating EMT and β-catenin signaling

“…β-Catenin signaling has been shown to be associated with the regulation of processes such as proliferation and invasion, which are involved in the occurrence and progression of cancers[ 27 , 28 ]. Moreover, the deactivation of β-catenin has been a potential treatment target in ESCC[ 29 - 31 ]. Thus, regulation of β-catenin may play an important role in the development of ESCC.…”

Natural biomolecules and derivatives as anticancer immunomodulatory agents

“…Since resistance to conventional chemotherapeutics is a major contributing factor to patient mortality, agents that sensitize resistant cells to chemotherapy or circumvent resistance altogether are of therapeutic value. Artemisinin acted synergistically with oxaliplatin to decrease tumor growth, migration and invasion of esophageal carcinoma ( 105 ). It also induced DNA damage, autophagy, cell cycle arrest and apoptosis in cisplatin-resistant breast cancer cells ( 106 ).…”

“…These results highlight the utility of ACTs not only as adjunct therapy, but as a natural biomolecule that can be utilized in drug hybridization to improve the potency and potentially reduce the resistance of standard chemotherapeutic agents. Furthermore, artemisinin and oxaliplatin synergistically decreased invasion, migration, and tumor growth of esophageal cancer cells ( 105 ).…”