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. 2021 May 26:12:681223.
doi: 10.3389/fphar.2021.681223. eCollection 2021.

"VSports app下载" Lidocaine Promoted Ferroptosis by Targeting miR-382-5p /SLC7A11 Axis in Ovarian and Breast Cancer

Dan Sun  1 , Ying-Chun Li  1 , Xiao-Yu Zhang  2
Affiliations

Lidocaine Promoted Ferroptosis by Targeting miR-382-5p /SLC7A11 Axis in Ovarian and Breast Cancer (V体育安卓版)

Dan Sun et al. Front Pharmacol. .

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 VSports手机版. 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. .

Keywords: SLC7A11; breast cancer; ferroptosis; lidocaine; miR-382-5p; ovarian cancer V体育安卓版. .

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

"VSports最新版本" Figures

FIGURE 1
FIGURE 1
Lidocaine induces ferroptosis of ovarian and breast cancer cells. (A,B) SKOV-3 and T47D cells were treated with lidocaine at the indicated concentrations. The mRNA expression of SLC7A11 was analyzed by qPCR. (C,D) SKOV-3 and T47D cells were co-treated with erastin (5 mmol/L) and lidocaine (3 mM). The cell viability was detected by MTT assays after 48 h of the treatment. (E–H) SKOV-3 and T47D cells were treated with lidocaine (3 mM). The Fe2+ (E), iron (Tesfay et al., 2019), and lipid ROS levels (G) were detected. (H) The expression of GPX4 and SLC7A11 was measured by Western blot analysis. The results were quantified using ImageJ software. mean ± SD, **p < 0.05, **p < 0.01. The experiments were performed independently three times.
FIGURE 2
FIGURE 2
Lidocaine reduces the proliferation of ovarian and breast cancer cells in vitro. (A–H) SKOV-3 and T47D cells were treated with lidocaine (3 mM). (A,B) The cell viability was detected by MTT assays. (C,D) The cell proliferation was measured by colony formation assays. (E,F) The apoptosis was analyzed by flow cytometry. (G) The expression of Bcl-2, Bax, caspase3, and cleaved-caspase3 was detected by Western blot. The results were quantified using ImageJ software. (H) The expression of RIPK3 was measured by Western blot. The results were quantified using ImageJ software. mean ± SD, **p < 0.01. The experiments were performed independently three times.
FIGURE 3
FIGURE 3
Lidocaine suppresses invasion and migration of ovarian and breast cancer cells in vitro. (A–D) SKOV-3 and T47D cells were treated with lidocaine (3 mM). (A,B) The cell invasion and migration were measured by transwell analysis. (C,D) The cell migration was analyzed by wound healing analysis. mean ± SD, **p < 0.01. The experiments were performed independently three times.
FIGURE 4
FIGURE 4
Lidocaine inhibits SLC7A11 expression by upregulating miR-382-5p. (A,B) SKOV-3 and T47D cells were treated with lidocaine (3 mM). The expression of miR-382-5p was analyzed by qPCR assays. (C–F) SKOV-3 and T47D cells were treated with miR-382-5p mimic. (C,D) The luciferase activity of SLC7A11 mRNA 3’UTR was analyzed. (E,F) The mRNA levels of SLC7A11 were examined by qPCR. (G) The protein expression of SLC7A11 was detected by Western blot analysis in SKOV-3 and T47D cells co-treated with lidocaine and miR-382-5p inhibitor. (H) The expression of miR-382-5p and SLC7A11 was detected by qPCR in clinical ovarian cancer tissues (n = 38) and breast cancer tissues (n = 50) and the related adjacent tissues. mean ± SD, **p < 0.01. The experiments were performed independently three times.
FIGURE 5
FIGURE 5
The inhibition of miR-382-5p blocks lidocaine-induced ferroptosis of ovarian and breast cancer cells. (A,B) The erastin (5 mmol/L) -stimulated SKOV-3 and T47D cells were co-treated with miR-382-5p inhibitor and lidocaine (3 mM). The cell viability was detected by MTT assays after 48 h of the treatment. (C–H) SKOV-3 and T47D cells were co-treated with miR-382-5p inhibitor and lidocaine. The Fe2+ (C,D), iron (E,F), and lipid ROS levels (G,H) were detected. mean ± SD, **p < 0.01. The experiments were performed independently three times.
FIGURE 6
FIGURE 6
Lidocaine/miR-382-5p axis reduces the proliferation of ovarian and breast cancer cells by targeting SLC7A11 in vitro. (A–D) SKOV-3 and T47D cells were co-treated with lidocaine (3 mM) and miR-382-5p inhibitor or SLC7A11 reconstitution vectors. (A,B) The cell viability was detected by MTT assays. (C,D) The apoptosis was analyzed by flow cytometry. mean ± SD, **p < 0.01. The experiments were performed independently three times.
FIGURE 7
FIGURE 7
Lidocaine attenuates proliferation of ovarian cancer cells in vivo. The nude mice were injected with SKOV-3 cells and treated with lidocaine (1.5 mg/kg). The tumor tissues (A), tumor volume (B), and tumor weight (C) were shown. (D) The expression of miR-382-5p was analyzed by qPCR assays. (E) The protein expression of SLC7A11 was detected by Western blot analysis. The results were quantified using ImageJ software. N = 5, mean ± SD, **p < 0.01.
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