Ovarian cancer has a high mortality rate among women worldwide. Radiotherapy is considered an effective method of ovarian cancer treatment, however, radioresistance presents a challenge. It is necessary to develop techniques that can increase radiosensitivity in ovarian cancer, and gene therapy is a promising option. The aim of the present study was to investigate the effects of metadherin (MTDH) silencing on the radiosensitivity of ovarian cancer. Ovarian cancer tissues (n=273) and normal ovarian tissues (n=277) were used, as were SKOV3 ovarian cancer cells and the immortalized human ovarian epidermal HOSEpiC cell line. MTT, Transwell and wound-healing assays were performed to assess the proliferation, invasion and migration abilities of the SKOV3 cells. Colony-forming assays and flow cytometry were applied to detect the radiosensitivity and apoptosis of the SKOV3 cells. Nude mouse xenograft models were established to evaluate the effect of MTDH gene silencing on tumor growth and the efficacy of radiotherapy. Ovarian cancer, in tissues and cells, was demonstrated to have a high level of MTDH. Additionally, MTDH silencing was found to significantly inhibit proliferation, migration and invasion, and induce apoptosis in SKOV3 cells, and it was suggested that MTDH depletion significantly increased the sensitivity of the SKOV3 cells to X-ray radiation. MTDH silencing enhanced radiosensitivity and delayed tumor growth in the nude mouse xenograft model. Collectively, the results obtained in the present study suggest the potential role of MTDH silencing as a technique for ameliorating radioresistance in ovarian cancer. The present study provides a promising experimental basis for the improvement of ovarian cancer radiotherapy treatment.
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http://dx.doi.org/10.3892/ijo.2018.4541 | DOI Listing |
B7-H3 (CD276), a member of the B7-family of immune checkpoint proteins, has been shown to have immunological and non-immunological effects promoting tumorigenesis [1, 2] and expression correlates with poor prognosis for many solid tumors, including cervical, ovarian and breast cancers [3-6]. We recently identified a tumor-cell autochthonous tumorigenic role for dimerization of the 4Ig isoform of B7-H3 (4Ig-B7-H3) [7], where 4Ig-B7-H3 dimerization activated tumor-intrinsic cellular proliferation and tumorigenesis pathways, providing a novel opportunity for therapeutic intervention. Herein, a live cell split-luciferase complementation strategy was used to visualize 4Ig-B7-H3 homodimerization in a high-throughput small molecule screen (HTS) to identify modulators of this protein-protein interaction (PPI).
View Article and Find Full Text PDFLiposomal doxorubicin (Dox), a treatment option for recurrent ovarian cancer, often suffers from suboptimal biodistribution and efficacy, which might be addressed with precision drug delivery systems. Here, we introduce a catheter-based endoscopic probe designed for multispectral, quantitative monitoring of light-triggered drug release. This tool utilizes red-light photosensitive porphyrin-phospholipid (PoP), which is encapsulated in liposome bilayers to enhance targeted drug delivery.
View Article and Find Full Text PDFFront Immunol
December 2024
Leeds Institute of Medical Research, School of Medicine, University of Leeds, St. James University Hospital, Leeds, United Kingdom.
Background: There has been limited success of cancer immunotherapies in the treatment of ovarian cancer (OvCa) to date, largely due to the immunosuppressive tumour microenvironment (TME). Tumour-associated macrophages (TAMs) are a major component of both the primary tumour and malignant ascites, promoting tumour growth, angiogenesis, metastasis, chemotherapy resistance and immunosuppression. Differential microRNA (miRNA) profiles have been implicated in the plasticity of TAMs.
View Article and Find Full Text PDFCell Commun Signal
January 2025
School of Medicine, Southeast University, Nanjing, Jiangsu, China.
Tribbles homolog 2 (TRIB2), a pseudoserine/threonine kinase, is a member of the TRIB family. TRIB2 primarily regulates cell proliferation through its scaffold or adaptor effect on promoting the degradation of target proteins by E3 ligase-dependent ubiquitination and regulating mitogen-activated protein kinase (MAPK) and protein kinase B (AKT) signaling pathways. TRIB2 is not only involved in the physiological proliferation of cells (granulosa cells, myoblasts, naive T cells, and thymocytes) during normal development but also in the pathological proliferation of vascular smooth muscle cells and a variety of cancer cells (lung cancer cells, liver cancer cells, leukemia cells, pancreatic cancer cells, gastric cancer cells, prostate cancer cells, thyroid cancer cells, cervical cancer cells, melanoma cells, colorectal cancer cells, ovarian cancer cells and osteosarcoma cells) under disease conditions.
View Article and Find Full Text PDFBMC Med
January 2025
Department of Gynaecology and Obstetrics, University and University Medical Center Schleswig-Holstein Campus Kiel, Kiel, Germany.
Ovarian cancer remains the most lethal gynecological malignancy. Despite the approval of promising targeted therapy such as bevacizumab and PARP inhibitors, 5-year survival has not improved significantly. Thus, there is an urgent need for new therapeutics.
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