Abstract
Gastric cancer is one of the most the prevalent malignancies and the therapeutic strategies for patients with gastric cancer remains limited. Local anesthetic levobupivacaine has demonstrated potential anti-cancer property, but its correlation with gastric cancer and ferroptosis is poor understood. Here, we identified the novel function of levobupivacaine in regulating ferroptosis of gastric cancer cells. The treatment of levobupivacaine suppressed gastric cancer cell viabilities and Edu-positive cell proportions. The gastric cancer cell growth was reduced by levobupivacaine in vivo. Moreover, the treatment of levobupivacaine enhanced erastin-induced inhibitory impact on gastric cancer cell viabilities. The levels of Fe2+/iron and lipid ROS were induced by levobupivacaine in erastin and RSL3-stimulated gastric cancer cells. levobupivacaine-upregulated miR-489-3p enhanced ferroptosis of gastric cancer cells by targeting SLC7A11. MiR-489-3p was involved in levobupivacaine-induced ferroptosis of gastric cancer cells. Levobupivacaine/miR-489-3p/SLC7A11 axis attenuates gastric cancer cell proliferation in vitro. Therefore, we concluded that the local anesthetic levobupivacaine induced ferroptosis of gastric cancer cells to repress gastric cancer cell growth by miR-489-3p/SLC7A11 axis.
Highlights
Gastric cancer is a lethal disease that ranks the fifth most prevalent cancer worldwide, often diagnosed at advanced stage (Smyth et al, 2020)
We initially evaluated the effect of levobupivacaine on cell growth of gastric cancer cells in vitro
We found that levobupivacaine did not affected the viability of normal gastric epithelial GES-1 cell lines but inhibited the viability of HGC27 and SGC7901 cells in a dosedependent manner (Figure 1A), and we selected the concentration of 2 mM in the subsequent analysis due to that 2 mM effectively repressed viability of HGC27 and SGC7901 cells and had no toxicity on GES-1 cells
Summary
Gastric cancer is a lethal disease that ranks the fifth most prevalent cancer worldwide, often diagnosed at advanced stage (Smyth et al, 2020). An increasing number of researches have demonstrated the involvement of ferroptosis in tumor development and drug-resistance of multiple cancer types, including gastric cancer (Yagoda et al, 2007; Alvarez et al, 2017; Zhang et al, 2020). Targeting ferroptosis may be an efficient therapeutic strategy for gastric cancer. Local anesthetics such as bupivacaine, levobupivacaine, and lidocaine, are indicated to be capable of affecting the progression of multiple cancers including gastric cancer, breast cancer and so on (Dan et al, 2018; Li et al, 2018). Castelli and colleagues recently reported that treatment with levobupivacaine led to the counteracted proliferation and migration of melanoma cells (Castelli et al, 2020). The function of levobupivacaine in gastric cancer is still unclear
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