HOTAIR Silencing Reduces Oxaliplatin Resistance in Gastric Cancer through PI3K/Akt Pathway

Abstract

Background: Oxaliplatin (OXA) is used to treat patients with advanced gastric cancer (GC). However, due to the presence of drug resistance, GC patients often respond poorly to chemotherapy. Methods: Quantitative real-time PCR (RT-qPCR) to detect HOX (homeobox) transcript antisense intergenic RNA (HOTAIR) expression in GC patients and OXA-resistant SGC-7901 cells. After HOTAIR silencing, Cell Counting Kit-8 (CCK-8), flow cytometry, wound-healing test, and Transwell® assay respectively measure cell proliferation, cell cycle and apoptosis, cell migration, and invasion ability. The p-PI3K, PI3K (phosphatidylinositol 3 kinase), p-ATK, ATK (protein kinase B), E-cadherin and Vimentin protein expression and their mRNA expression levels were tested by Western blotting and RT-qPCR. In addition, a xenograft tumor experiment was conducted to further verify the role of HOTAIR in GC. Results: In this study, we observed that HOTAIR was highly expressed in GC patients and OXA-resistant SGC-7901 cells. HOTAIR silencing significantly reduced the proliferation, migration and invasion ability of SGC-7901 and OXA-resistant SGC-7901 cells, increased the apoptosis rate, and arrested cells at the G2 phase. In vivo research revealed that HOTAIR knockdown significantly inhibited tumor development. Silencing HOTAIR inhibited phosphatidylinositol 3 kinase (PI3K)/protein kinase B (AKT) signaling pathway while decreasing the expression of Vimentin, p-Akt and p-PI3K, and increasing the expression of E-cadherin. Overall, HOTAIR silencing inhibits epithelial-mesenchymal transition (EMT) through the PI3K/Akt pathway to inhibit OXA resistance in GC. Conclusions: HOTAIR might be a potential novel therapeutic target for GC that is OXA-resistant.