AI Article Synopsis
- About 40% of patients with advanced ovarian cancer survive beyond 5 years, prompting research into effective treatments.
- Previous studies indicate that pitavastatin can reduce ovarian cancer growth in mice, leading to further investigation on its effectiveness when combined with other drugs like zoledronic acid and GGTI-2133.
- The findings show that pitavastatin combined with zoledronic acid enhances the anticancer effects by improving cell sensitivity, suggesting this combination could be a promising option for treating ovarian cancer.
Article Abstract
Only 40% of patients with advanced ovarian cancer survive more than 5 years. We have previously shown that pitavastatin induces regression of ovarian cancer xenografts in mice. To evaluate whether the response of ovarian cancer cells to pitavastatin is potentiated by farnesyl diphosphate synthase inhibitors or geranylgeraniol transferase I inhibitors, we evaluated combinations of pitavastatin with zoledronic acid, risedronate and GGTI-2133 in a panel of ovarian cancer cells. Pitavastatin (IC = 0.6-14 μM), zoledronic acid (IC = 21-57 μM), risedronate (IC > 100 μM) or GGTI-2133 (IC > 25 μM) inhibited the growth of ovarian cancer cell cultures. Combinations of pitavastatin with zoledronic acid displayed additive or synergistic effects in cell growth assays in 10 of 11 cell lines evaluated as well as in trypan blue exclusion, cellular ATP or caspase 3/7, 8 and 9 assays. Pitavastatin reduced levels of GGT-IIβ and the membrane localization of several small GTPases and this was potentiated by zoledronic acid. siRNA to GGT-Iβ and GGT-IIβ used in combination, but not when used individually, significantly increased the sensitivity of cells to pitavastatin. These data suggest that zoledronic acid, a drug already in clinical use, may be usefully combined with pitavastatin in the treatment of ovarian cancer.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5556066 | PMC |
| http://dx.doi.org/10.1038/s41598-017-08649-9 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Bola-Amphiphilic Dendrimer Enhances Imatinib to Target Metastatic Ovarian Cancer via β-Catenin-HRP2 Signaling Axis.
ACS Appl Mater Interfaces
January 2025
School of Biological Sciences, University of Hong Kong, Pokfulam, Hong Kong 999077, China.
Ovarian cancer is the leading cause of death among all gynecological malignancies, and drug resistance renders the current chemotherapy agents ineffective for patients with advanced metastatic tumors. We report an effective treatment strategy for targeting metastatic ovarian cancer involving a nanoformulation (Bola/IM)─bola-amphiphilic dendrimer (Bola)-encapsulated imatinib (IM)─to target the critical mediator of ovarian cancer stem cells (CSCs) CD117 (c-Kit). Bola/IM offered significantly more effective targeting of CSCs compared to IM alone, through a novel and tumor-specific β-catenin/HRP2 axis, allowing potent inhibition of cancer cell survival, stemness, and metastasis in metastatic and drug-resistant ovarian cancer cells.
View Article and Find Full Text PDFThe molecular mechanism of gemcitabine in inhibiting the HIF-1α/VEGFB/FGF2/FGFR1 signaling pathway for ovarian cancer treatment.
Discov Oncol
January 2025
Department of Oncology and Gynecology, The First Affiliated Hospital of Bengbu Medical University, No. 287, Changhuai Road, Longzihu District, Bengbu, Anhui, China.
Ovarian cancer is a common malignant tumor in women, exhibiting a certain sensitivity to chemotherapy drugs like gemcitabine (GEM). This study, through the analysis of ovarian cancer single-cell RNA sequencing (scRNA-seq) data and transcriptome data post-GEM treatment, identifies the pivotal role of hypoxia-inducible factor 1 alpha (HIF-1α) in regulating the treatment process. The results reveal that HIF-1α modulates the expression of VEGF-B, thereby inhibiting the fibroblast growth factor 2 (FGF2)/FGFR1 signaling pathway and impacting tumor formation.
View Article and Find Full Text PDFTertiary lymphoid structures in high-grade serous tubo-ovarian carcinoma: anatomical site matters.
Cancer Immunol Immunother
January 2025
Division of Oncology, Department of Clinical Sciences Lund, and Lund University Cancer Center, Lund University, Lund, Sweden.
Tertiary lymphoid structures (TLS) in the tumor microenvironment are prognostically beneficial in many solid cancer types. Reports on TLS in high-grade serous tubo-ovarian carcinoma (HGSC) are few, and the prognostic impact is unclear. We investigated mature TLS (mTLS), immature TLS (iTLS) and lymphoid aggregates (LA) in primary adnexal tumors (PTs) and synchronous omental/peritoneal metastases (pMets) of HGSC.
View Article and Find Full Text PDFTissue factor targeted near-infrared photoimmunotherapy: a versatile therapeutic approach for malignancies.
Cancer Immunol Immunother
January 2025
Molecular Imaging Branch, Center for Cancer Research, National Cancer Institute, NIH, 10 Center Drive, Bethesda, MD, 20892, USA.
Tissue factor (TF) is a cell surface protein that plays a role in blood clotting but is also commonly expressed in many cancers. Recent research implicated TF in cancer proliferation, metastasis, angiogenesis, and immune escape. Therefore, TF can be considered a viable therapeutic target against cancer.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!