Qing Liu

Hypoxia-driven remodeling of SELENOP+ macrophages shapes T cell dynamics and promotes ovarian cancer metastasis

Abstract High-grade serous ovarian cancer (HGSOC) is characterized by extensive transcoelomic dissemination and the accumulation of ascites. However, how site-specific tumor microenvironment (TME) drives progression remains unknown. Here we show the co-occurrence and spatial co-localization of SELENOP + macrophages and precursor exhausted CD8 + T cells and demonstrate that SELENOP + macrophages activate T cells via selenoprotein P in vitro and in vivo. We further identify a dynamic transition in the SELENOP + / SPP1 + macrophage populations as tumor metastasis, driven by increased hypoxia malignant epithelial cells through VEGFA-EPHB2 signaling. We also reveal that anti-VEGFA intervention controls ovarian tumor growth by increasing SELENOP + macrophages and cytotoxicity of CD8 + T cells in vivo. Taken together, these findings spotlight the role of tumor-induced TME remodeling in subverting immune-mediated tumor control and thus facilitating HGSOC metastasis in females. Collectively, our results provide a foundation for the development of targeted therapeutic interventions aimed at impeding HGSOC metastatic trajectory.

Melittin suppresses ovarian cancer growth by regulating SREBP1-mediated lipid metabolism

Melittin, a major peptide component of bee venom, has demonstrated promising anti-cancer activity across various preclinical cell models, making it a potential candidate for cancer therapy. However, its molecular mechanisms, particularly in ovarian cancer, remain largely unexplored. Ovarian cancer is a life-threatening gynecological malignancy with poor clinical outcomes and limited treatment options. This study evaluated the efficacy of melittin in suppressing ovarian cancer and elucidated its underlying molecular mechanisms. A subcutaneous xenograft tumor model was established using ID8 cells in C57BL/6J mice. RNA sequencing revealed that melittin's anticancer effects were associated with the downregulation of lipid metabolism, particularly fatty acid synthesis. The impact of melittin on de novo fatty acid synthesis was assessed by measuring free fatty acid (FFA), triglyceride (TG), and total cholesterol (TC) levels in ovarian cancer cells. Lipogenic gene expression and sterol regulatory element-binding protein 1 (SREBP1) were analyzed by Western blot and quantitative real-time polymerase chain reaction. The regulation of FASN transcription by SREBP1 was explored using a dual-luciferase reporter assay. Plasmid DNA transfection and the SREBP1 inhibitor Fatostatin were employed to identify the signaling pathway mediating melittin's anticancer effects. Our results confirmed that melittin significantly reduced de novo fatty acid synthesis, as evidenced by lower FFA, TG, and lipid droplet levels. Additionally, melittin inhibited the nuclear translocation of SREBP1 and specifically reduced SREBP1-mediated FASN transcription, demonstrating effects similar to those of Fatostatin. The motif (-424/-415) within the FASN promoter is a potential SREBP-1 binding site. SREBP1 overexpression through plasmid DNA transfection significantly counteracted melittin's downregulation of FASN promoter activity and counteracted its inhibitory effects on de novo fatty acid synthesis, cell proliferation, and colony formation. Our findings suggested that melittin acts as a novel modulator of the SREBP1/FASN pathway, reducing lipogenesis and inhibiting ovarian cancer growth. This study was the first to demonstrate melittin's ability to target the SREBP1/FASN axis in ovarian cancer, identifying SREBP1 as a novel therapeutic target. These results highlighted melittin as a potential therapeutic agent for ovarian cancer by attenuating SREBP1-mediated lipid metabolism and suggested novel treatment strategies for targeting ovarian cancer.

Protection motivation theory in predicting cervical cancer screening participation: A longitudinal study in rural Chinese women

AbstractObjectiveTo examine factors longitudinally associated with cervical cancer screening uptake among rural Chinese women, guided by protection motivation theory (PMT).MethodsA large sample of women (n = 2408, aged 35‐65 years old) was randomly selected from a rural county in China in 2015 and followed up for 2 years. Data for demographic factors, knowledge of cervical cancer screening, screening outcome, and six PMT constructs measured at the baseline in 2015 were used to predict cervical cancer screening participation at the follow‐up in 2017 using structural equation model method.ResultsAmong the 2408 women at the baseline, 1879 (78.03%) participated in the screening services at the follow‐up. In addition to significant direct effect of age, social status and baseline screening outcome, and three (perceived severity, fear arousal and response efficacy) of the six PMT subconstructs, four variables (age, social status, knowledge of cervical cancer screening, and baseline screening outcome) at the baseline were indirectly associated with screening participation, mediated by the three significant PMT subconstructs.ConclusionsFindings of this study indicate that the rate of participating in cervical cancer screening for rural women needs to be further improved. In addition to the commonly reported influential factors, PMT subconstructs play important roles in encouraging rural women in China to participate in cervical cancer screening. These longitudinal findings provided data much needed for future research to develop evidence‐based intervention programs to enhance cervical cancer screening among rural women in China.