The CXCLs-CXCR2 axis modulates the cross-communication between tumor-associated neutrophils and tumor cells in cervical cancer.

OBJECTIVE: This study aimed to check the expression profile of the C-X-C motif chemokine ligands (CXCLs)-C-X-C motif chemokine receptor 2 (CXCR2) axis in cervical cancer and to explore the cross-talk between cervical cancer cells and neutrophils via CXCLs-CXCR2 axis. METHODS: Available RNA-sequencing data based on bulk tissues and single-cell/nucleus RNA-sequencing data were used for bioinformatic analysis. Cervical cancer cell lines Hela and SiHa cells were utilized for in vitro and in vivo studies. RESULTS: Except for neutrophils, CXCR2 mRNA expression is limited in other types of cells in the cervical tumor microenvironment. CXCLs bind to CXCR2 and are mainly expressed by tumor cells. CXCL1, 2, 3, 5, 6, and 8, which are consistently associated with neutrophil infiltration, are also linked to poor prognosis. SB225002 (a CXCR2 inhibitor) treatment significantly impairs SiHa cell-induced neutrophil migration. CXCL1, CXCL2, CXCL5, or CXCL8 neutralized conditioned medium from SiHa cells have weaker recruiting effects. The conditioned medium of neutrophils from healthy donors can slow cancer cell proliferation. Conditioned medium of tumor-associated neutrophils (TANs) can drastically enhance cervical cancer cell growth in vitro and in vivo. CONCLUSIONS: The CXCLs-CXCR2 axis is critical in neutrophil recruitment and tumor cell proliferation in the cervical cancer microenvironment.

CXCL8 Promotes Endothelial-to-Mesenchymal Transition of Endothelial Cells and Protects Cells from Erastin-Induced Ferroptosis via CXCR2-Mediated Activation of the NF-κB Signaling Pathway.

CXCL8-CXCR1/CXCR2 signaling pathways might form complex crosstalk among different cell types within the ovarian tumor microenvironment, thereby modulating the behaviors of different cells. This study aimed to investigate the expression pattern of CXCL8 in the ovarian tumor microenvironment and its impact on both endothelial-to-mesenchymal transition (EndMT) and ferroptosis of endothelial cells. The human monocytic cell line THP-1 and the human umbilical vein endothelial cell line PUMC-HUVEC-T1 were used to conduct in vitro studies. Erastin was used to induce ferroptosis. Results showed that tumor-associated macrophages are the major source of CXCL8 in the tumor microenvironment. CXCL8 treatment promoted the nucleus entrance of NF-κB p65 and p65 phosphorylation via CXCR2 in endothelial cells, suggesting activated NF-κB signaling. Via the NF-κB signaling pathway, CXCL8 enhanced TGF-ß1-induced EndMT of PUMC-HUVEC-T1 cells and elevated their expression of SLC7A11 and GPX4. These trends were drastically weakened in groups with CXCR2 knockdown or SB225002 treatment. TPCA-1 reversed CXCL8-induced upregulation of SLC7A11 and GPX4. CXCL8 protected endothelial cells from erastin-induced ferroptosis. However, these protective effects were largely canceled when CXCR2 was knocked down. In summary, CXCL8 can activate the NF-κB signaling pathway in endothelial cells in a CXCR2-dependent manner. The CXCL8-CXCR2/NF-κB axis can enhance EndMT and activate SLC7A11 and GPX4 expression, protecting endothelial cells from ferroptosis.

Effects of bushen zhuyun decoctlon on the reproductive capacity of mice: an experimental research / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To study the effects of Bushen Zhuyun Decoction (BZD) on the reproductive capacity of mice.</p><p><b>METHODS</b>Totally 60 female Kunming mice were randomly divided into the experimental group and the control group. BZD was perfused by gastric tube to mice in the experimental group, twice daily. Meanwhile, mice in the control group were administered with normal saline by gastrogavage. Mice were sacrificed on the 10th day and the 20th day of medication respectively, 15 mice each time in each group. The serum levels of estradiol and progesterone were detected by radioimmunoassay. The morphological changes of uterus and ovary were observed using HE staining. The expressions of leukaemia inhibitory factor (LIF), epidermal growth factor (EGF), and calcitionin (CT) were determined using immunohistochemical assay.</p><p><b>RESULTS</b>Compared with the control group at the same time point, the weights of uterus and ovary increased, the serum levels of estradiol and progestogen increased, the expressions of LIF, CT, and EGF increased in the experimental group on the 10th day and the 20th day of medication (P <0.05, P <0.01). Better results were shown on the 20th day of medication (P <0.05). Histological results showed increased ovarian follicle numbers, increased endometrial gland numbers, endometrial hyperplasia (stratiform arranged), and increased stromal cells in the experimental group, especially on the 20th day of medication.</p><p><b>CONCLUSION</b>BZD could improve the reproductive capacity by advancing the development of generative organs, promoting the secretion of estradiol and progestogen and the follicular growth, and increasing the receptivity of endometrium.</p>