Apatinib inhibits gastric carcinoma development by regulating the expression levels of IL‑17 via the Bax/Bcl‑2 signaling pathway

Abstract

Gastric carcinoma is a common type of gastrointestinal tumor with high morbidity and mortality rates. IL-17 is a newly discovered cytokine that has been reported to serve an important role in the development of gastric carcinoma. The potential effect of apatinib on IL-17 expression levels in the development of gastric carcinoma has been rarely reported. The present study aimed to investigate the potential mechanism of IL-17 and apatinib in the development of gastric carcinoma. A total of 30 tumor and para-carcinoma tissues were collected from 30 patients with gastric carcinoma between January 2019 and December 2019 and the expression levels of IL-17 in the tissues were analyzed by reverse transcription-quantitative PCR and western blotting. An in vitro model of gastric carcinoma was also established using the HGC-27 cell line, in which the cells were divided into control, IL-17, IL-17-apatinib and apatinib groups. The expression levels of IL-17, Bax, Bcl-2 and caspase-3 were analyzed using reverse transcription-quantitative PCR and western blotting. An MTT assay and flow cytometry were used to analyze the proliferation and apoptosis of HGC-27 cells, respectively, and a Transwell assay was used to analyze the invasive ability of HGC-27 cells. The results revealed that the expression levels of IL-17 were significantly upregulated in the gastric carcinoma tissues compared with the para-carcinoma tissues. In vitro, IL-17 treatment promoted the proliferation and invasive ability of HGC-27 cells, but inhibited the apoptosis with the significantly downregulated expression levels of Bax and caspase-3 and the upregulated expression levels of Bcl-2 than control group. Conversely, apatinib treatment significantly inhibited the proliferative and invasive abilities of HGC-27 cells, but promoted cell apoptosis in the IL-17 and IL-17-apatinib groups.. Collectively, the present results suggested that the upregulation of IL-17 may be associated with the occurrence and development of gastric carcinoma. The findings indicated that apatinib may inhibit gastric carcinoma development by regulating IL-17 expression via the Bax/Bcl-2 signaling pathway. Therefore, the present findings may enhance the current knowledge of the effect of apatinib on gastric carcinoma cells.

Apatinib weakens proliferation, migration, invasion, and angiogenesis of thyroid cancer cells through downregulating pyruvate kinase M2

“…no. S5248) for 48 h 51 . PKM2 overexpression plasmid and empty vector, PKM2 shRNAs and control were provided by Integrated Biotech Solutions (Shanghai, China).…”

The IL-17 family in diseases: from bench to bedside

“… 300 IL-17-mediated signaling is associated with the migration and invasion of various malignant tumors, including oral squamous cell carcinoma, 23 breast cancer, 24 and gastric cancer. 25 In addition, EMT can effectively promote tumor metastasis, recurrence, and drug resistance by enhancing the stem cell properties and mobility of tumor cells. In recent years, IL-17-mediated CSC formation 161 , 301 and EMT-like alterations have been suggested to be essential for tumor migration and invasion.…”

“… 17 In recent years, the association between IL-17 and tumors has been extensively studied. 23 – 25 However, a more comprehensive understanding of the mechanisms of IL-17 signal transduction is required to improve the efficacy of IL-17-related therapies in treating inflammatory and autoimmune diseases and for the precise treatment of tumors.…”