Abstract
Ovarian and breast cancer are prevalent female malignancies with increasing occurrence incidence and metastasis, significantly affecting the health and life quality of women globally. Anesthetic lidocaine has presented anti-tumor activities in the experimental conditions. However, the effect of lidocaine on ovarian and breast cancer remains elusive. We identified the important function of lidocaine in enhancing ferroptosis and repressing progression of ovarian and breast cancer. Our data showed that lidocaine further repressed erastin-inhibited ovarian and breast cancer cell viabilities. The treatment of lidocaine induced accumulation of Fe2+, iron and lipid reactive oxygen species (ROS) in ovarian and breast cancer cells. The ovarian and breast cancer cell proliferation was suppressed while cell apoptosis was induced by lidocaine in vitro. Lidocaine attenuated invasion and migration of ovarian and breast cancer cells as well. Regarding the mechanism, we found that lidocaine downregulated solute carrier family 7 member 11 (SLC7A11) expression by enhancing microRNA-382-5p (miR-382-5p) in the cells. The inhibition of miR-382-5p blocked lidocaine-induced ferroptosis of ovarian and breast cancer cells. MiR-382-5p/SLC7A11 axis was involved in lidocaine-mediated inhibition of ovarian and breast cancer cell proliferation in vitro. The miR-382-5p expression was down-regulated but SLC7A11 expression was up-regulated in clinical ovarian and breast cancer samples. Furthermore, the treatment of lidocaine repressed tumor growth of ovarian cancer cells in vivo, in which the miR-382-5p expression was increased while SLC7A11 expression was decreased. Consequently, we concluded that the lidocaine promoted ferroptosis by miR-382-5p/SLC7A11 axis in ovarian and breast cancer cells. The clinical value of lidocaine in the treatment of ovarian and breast cancer deserves to be proved in detail.
Highlights
Breast cancer and ovarian cancer are the most frequently occurred gynecological cancers globally, severely threatened the life quality of females
Despite the anesthetic lidocaine has been identified to present potential anti-tumor effects, the functions of lidocaine in ovarian and breast cancer are unclear
We reported a critical role of lidocaine in modulating ferroptosis of ovarian and breast cancer cells
Summary
Breast cancer and ovarian cancer are the most frequently occurred gynecological cancers globally, severely threatened the life quality of females (de Sousa Cunha et al, 2019; Siegel et al, 2020). Breast cancer has gain great attentions caused by its constantly increasing incidence despite of the improvement in treatment (Britt et al, 2020). Ovarian cancer represents a major clinical challenge due to the frequent late diagnosis at advanced tumor stage (Jayson et al, 2014). Lidocaine in Ovarian and Breast Cancer reactive oxygen species (ROS) (Dixon et al, 2012). Accumulating studies have indicated that targeting ferroptosis may be a feasible strategy for therapy of breast cancer and ovarian cancer (Li et al, 2020). It was proposed that triple negative breast cancer (TNBC) patients were more sensitive to ferroptosis than estrogen receptor (Wang et al, 2021)-positive patients, which provided a potential therapeutic strategy for TNBC patients (Doll et al, 2017). Ferroptosis mediated platinum tolerance in ovarian cancer (Wang et al, 2021)
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