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

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 (R) assay respectively measure cell proliferation, cell cycle and apoptosis, cell migra-tion, 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. HO-TAIR 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 signif-icantly 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.

Automated summary

In this study, HOTAIR was found to be highly expressed in patients with gastric cancer and OXA-resistant cells. Silencing HOTAIR significantly inhibited the proliferation, migration, and invasion ability of gastric cancer cells, increased apoptosis rate, and arrested cells in the G2 phase. Furthermore, HOTAIR silencing inhibited the PI3K/Akt signaling pathway and epithelial-mesenchymal transition process, leading to the inhibition of OXA resistance in gastric cancer.