Ovarian cancer (OC) remains one of the leading causes of cancer-related mortality among women. Targeting the insulin-like growth factor 1 (IGF-1) signaling pathway has emerged as a promising therapeutic strategy. Linsitinib, an IGF-1 receptor (IGF-1R) inhibitor, has shown potential in disrupting this pathway. Additionally, metformin, commonly used in the treatment of type 2 diabetes, has been studied for its anti-cancer properties due to its ability to inhibit metabolic pathways that intersect with IGF-1 signaling, making it a candidate for combination therapy in cancer treatments. This study explores the anti-cancer effects of linsitinib and metformin on OVCAR3 cells by the suppression of the IGF-1 signaling pathway by siRNA-mediated gene silencing. The goal is to evaluate their efficacy as therapeutic agents and to emphasize the critical role of this pathway in OC cell proliferation. Cellular viability was evaluated by resazurin-based assay, and apoptosis was assessed by flux cytometry. The results of this study indicate that the combination of linsitinib and metformin exhibits an antagonistic effect (obtained by SynergyFinder 2.0 Software), reducing their anti-neoplastic efficacy in OC cell lines. Statistical analyses were performed using ordinary one-way or two-way ANOVA, followed by Tukey's or Šídák's multiple comparison tests. While linsitinib shows promise as a therapeutic option for OC, further research is needed to identify agents that could synergize with it to enhance its therapeutic efficacy, like the combination with standard chemotherapy in OC (carboplatin and paclitaxel).
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http://dx.doi.org/10.3390/ijms252211935 | DOI Listing |
Arch Osteoporos
December 2024
Department of Pharmacology, Faculty of Medicine, Chiang Mai University, Chiang Mai, 50200, Thailand.
Unlabelled: This study examined how isoflavone interventions impact bone health in postmenopausal women. Analyzing 73 trials found that isoflavones reduce bone resorption markers, enhance bone minerals, and increase hormones regulating bone metabolism. This suggests that isoflavones could help address bone health issues in postmenopausal women.
View Article and Find Full Text PDFJ Drug Target
December 2024
Department of Pharmaceutics, School of Pharmacy & Technology Management, SVKM'S Narsee Monjee Institute of Management Studies, Shirpur-425405, Maharashtra, India.
The occurrence of oral bone tissue degeneration and bone defects by osteoporosis, tooth extraction, obesity, trauma, periodontitis, and congenital defects are major challenges for clinicians. Traditional bone regeneration methods, although exhibiting efficacy to a certain degree, often come with limitations such as donor site morbidity, limitation of special shape, inflammation, and resorption of the implanted bone. The treatment oriented with biomimetic bone materials has achieved significant attention recently.
View Article and Find Full Text PDFPLoS One
December 2024
Department of Ophthalmology and Visual Science, Yeouido St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea.
Thyroid-associated ophthalmopathy (TAO), an autoimmune disorder of the retrobulbar tissue, is present in up to 50 percent of Graves's hyperthyroidism patients. Insulin-like growth factor 1 receptor (IGF-1R) has received attention as a target for the development of therapeutic agent for TAO. IGF-1R and TSHR (thyroid stimulating hormone receptor) interact with each other to form a physical or functional complex, further promoting the development of TAO.
View Article and Find Full Text PDFFront Physiol
December 2024
Laboratory of Molecular Biology, Institute of Physiotherapy and Health Sciences, Academy of Physical Education, Katowice, Poland.
Over the past couple of decades, it has become apparent that skeletal muscles might be engaged in endocrine signaling, mostly as a result of exercise or physical activity in general. The importance of this phenomenon is currently studied in terms of the impact that exercise- or physical activity -induced signaling factors have, in the interaction of the "muscle-brain crosstalk." So far, skeletal muscle-derived myokines were demonstrated to intercede in the connection between muscles and a plethora of various organs such as adipose tissue, liver, or pancreas.
View Article and Find Full Text PDFInt J Mol Sci
December 2024
College of Life Sciences, Nankai University, Tianjin 300071, China.
Hesperetin (Hst) is a common citrus fruit flavonoid with antioxidant, anti-inflammatory, and anti-neurodegenerative effects. To explore the antioxidant and anti-aging effects and mechanisms of Hst, we induced chronic oxidative stress in using low-concentration HO and examined its effects on lifespan, healthy life index, reactive oxygen species (ROS), antioxidant enzymes, and transcriptomic metrics. Hst significantly prolonged lifespan, increased body bending and pharyngeal pumping frequency, decreased ROS accumulation, and increased antioxidant enzyme activity in normal and stressed .
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