ABSTRACT
Ovarian cancer is a highly lethal gynecological malignancy, emphasizing the need for effective treatment strategies. This study investigated the synergistic effects of quercetin and paclitaxel on ovarian cancer. Using SKOV3 and A2780 cell lines, we found that the combined treatment significantly enhanced cell apoptosis and inhibited invasion and migration compared to individual treatments. Then, we identified 32 common targets between quercetin/paclitaxel and ovarian cancer, with 29 genes showing differential expression between normal ovarian tissue and ovarian tumor tissue. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses revealed that quercetin and paclitaxel modulated cancer-related pathways in ovarian cancer treatment. Mechanistic analysis further discovered that the synergistic effect was mediated by downregulating ERBB2 and BIRC5 and upregulating CASP3 expression. This study provides strong evidence that quercetin enhances the effectiveness of paclitaxel in treating ovarian cancer.
ABSTRACT
Cervical cancer poses a serious threat to women's health globally. Our previous studies found that upregulation of TM7SF2, which works as an enzyme involved in the process of cholesterol biosynthesis expression, was highly correlated with cervical cancer. However, the mechanistic basis of TM7SF2 promoting cervical cancer progression via lipid metabolism remains poorly understood. Therefore, quantification of fatty acids and lipid droplets were performed in vitro and in vivo. The protein-protein interaction was verified by Co-IP technique. The mechanism and underlying signaling pathway of TM7SF2 via CPT1A associated lipid metabolism in cervical cancer development were explored using Western blotting, IHC, colony formation, transwell assay, and wound healing assay. This study reported that overexpression of TM7SF2 increased fatty acids content and lipid droplets both in vivo and in vitro experiments. While knockout of TM7SF2 obviously attenuated this process. Moreover, TM7SF2 directly bonded with CPT1A, a key enzyme in fatty acid oxidation, and regulated CPT1A protein expression in cervical cancer cells. Notably, the proliferation and metastasis of cervical cancer cells were elevated when their CPT1A expression was upregulated. Then, rescue assay identified that CPT1A overexpressed could enhance the cell viability and migration in TM7SF2-knockout cells. Furthermore, depletion of TM7SF2 significantly inhibited WNT and ß-catenin proteins expression, which was enhanced by CPT1A-overexpressed. The proliferation and migration of cervical cancer cells were reversed in CPT1A-overexpressed cells with the treatment of MSAB, an inhibitor of Wnt/ß-Catenin pathway. This study put forward an idea that TM7SF2-induced lipid reprogramming promotes proliferation and migration via CPT1A/Wnt/ß-Catenin axis in cervical cancer, underlying the progression of cervical cancer.
ABSTRACT
Cervical cancer (CC) is a common gynecological malignancy. Despite the current screening methods have been proved effectively and significantly decreased CC morbidity and mortality, deficiencies still exist. Single-cell RNA sequencing (scRNA-seq) approach can identify the complex and rare cell populations at single-cell resolution. By scRNA-seq, the heterogeneity of tumor microenvironment across cervical carcinogenesis has been mapped and described. Whether these alterations could be detected and applied to CC screening is unclear. Herein, we performed scRNA-seq of 56,173 cervical exfoliated cells from 15 samples, including normal cervix, low-grade squamous intraepithelial lesion (LSIL), high-grade squamous intraepithelial lesion (HSIL), and malignancy. The present study delineated the alteration of immune and epithelial cells derived during the cervical lesion progression. A subset of lipid-associated macrophage was identified as a tumor-promoting element and could serve as a biomarker for predicting the progression of LSIL into HSIL, which was then verified by immunofluorescence. Furthermore, cell-cell communication analysis indicated the SPP1-CD44 axis might exhibit a protumor interaction between epithelial cell and macrophage. In this study, we investigated the cervical multicellular ecosystem in cervical carcinogenesis and identified potential biomarkers for early detection.
Subject(s)
Carcinoma, Squamous Cell , Papillomavirus Infections , Uterine Cervical Dysplasia , Uterine Cervical Neoplasms , Female , Humans , Cervix Uteri/pathology , Uterine Cervical Dysplasia/diagnosis , Uterine Cervical Dysplasia/pathology , Ecosystem , Papillomavirus Infections/pathology , Uterine Cervical Neoplasms/genetics , Uterine Cervical Neoplasms/pathology , Carcinoma, Squamous Cell/pathology , Biomarkers, Tumor/genetics , Carcinogenesis/genetics , Carcinogenesis/pathology , Sequence Analysis, RNA , Tumor Microenvironment/geneticsABSTRACT
Effective manipulation of magnetic properties in transition-metal oxides is one of the crucial issues for the application of materials. Up to now, most investigations have focused on electrolyte-based ionic control, which is limited by the slow speed. In this work, the interfacial coupling of the SrCoO2.5/La0.7Ca0.3MnO3 (LCMO) bilayer is effectively modulated with fast response time. After being treated with diluted acetic acid, the bilayer changes from antiferromagnetic/ferromagnetic (AFM/FM) coupling to FM/FM coupling and the Curie temperature is also effectively increased. Meanwhile, the corresponding electric transport properties are modulated within a very short time. Combined with the structure characterization and X-ray absorption measurements, we find that the top SrCoO2.5 layer is changed from the antiferromagnetic insulator to the ferromagnetic metal phase, which is attributed to the formation of the active oxygen species due to the reaction between the protons in the acid and the SrCoO2.5 layer. The bottom LCMO layer remains unchanged during this process. The response time of the bilayer with the acid treatment method is more than an order of magnitude faster than other methods. It is expected that this acid treatment method may open more possibilities for manipulating the magnetic and electric properties in oxide-based devices.