Targeted Detection of Cyclooxygenase-1 in Ovarian Cancer.
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ABSTRACT:
SUBMITTER: Malerba P
PROVIDER: S-EPMC7549111 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Ovarian cancer (OC) is the sixth and eighth leading cause of cancer mortality among women in developed and developing countries, respectively. Medical therapy is the main method for the treatment of OC. However, drug toxicity and the marked side effects of chemotherapy limit the usage and therapeutic results of the treatments. Therefore, the identification of multi-target agents with few side effects and high effectiveness is required. Traditional Chinese medicine has been used clinically to treat various types of cancer for thousands of years and is considered to possess multiple components and agents, which exert efficient therapeutic functions with few side effects. Although blueberries have previously been used to treat various types of cancer, the effect on OC and precise molecular mechanism of function of the fruit remains unknown. Cyclooxygenase (COX)-1 and COX-2 have been reported to be the biomarkers of OC. Blueberries may affect the progression of OC by affecting COX levels. To investigate the issue, COX-1 and COX-2 were overexpressed or silenced in ovarian cancer SKOV3 cells. The effect of blueberries on SKOV3 cell viability was determined by an MTT assay. Furthermore, a mouse model for OC was established. The results indicated that blueberries inhibited the proliferation of OC cells by downregulating the levels of COX-1 and COX-2. Blueberry (400 mg daily) consumption reduced tumor size significantly in mice with OC compared with the control without blueberry treatment (P<0.05). The results suggest that blueberries should be used to develop a potential non-pharmaceutical therapy for OC.
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Project description:Metastatic ovarian cancer, the most lethal of gynecologic malignancies, is typically managed by debulking surgery, followed by chemotherapy. However, despite significant efforts, survival rate remains low. We have previously demonstrated, in mouse models, a specific systemic homing of labeled fibroblasts to solid ovarian tumors. Here, we demonstrate the feasibility of utilizing this specific homing of genetically modified fibroblasts for detection and targeted therapy of orthotopic metastatic ovarian carcinoma model in immune-deficient mice. Using an in vivo metastatic mouse model for ovarian cancer, we demonstrated that fibroblasts expressing fluorescent reporters injected intra-peritoneally, were specifically recruited to peritoneal tumor nodules (resulting in 93-100% co-localization). We further used fibroblasts over expressing the soluble receptor variant of VEGFR1 (s-Flt1). Mice bearing tumors were injected weekly with either control or s-Flt1 expressing fibroblasts. Injection of s-Flt1 expressing fibroblasts resulted in a significant reduction in the ascites volume, reduced vascularization of adherent metastases, and improved overall survival. Using fluorescently labeled fibroblasts for tumor detection with readily available intra-operative fluorescence imaging tools may be useful for tumor staging and directing biopsies or surgical efforts during exploratory or debulking surgery. Fibroblasts may serve as a beacon pointing to the otherwise invisible metastases in the peritoneal cavity of ovarian cancer patients. Utilizing the recruited fibroblasts also for targeted delivery of anti angiogenic or antitumor molecules may aid in controlling tumor progression. Thus, these results suggest a novel approach for targeting ovarian tumor metastases for both tumor detection and therapy.
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