Characterized by autophagy-associated protein disorders, autophagy participates in Taxol resistance in triple negative breast cancer (TNBC). As an evolutionarily conserved serine/threonine protein kinase with complex signaling pathway, mammalian target of rapamycin (mTOR) can regulate various cellular functions by phosphorylation of its downstream target proteins after activation. A large number of references have demonstrated that mTOR signaling pathway is related to autophagy and apoptosis. Formononetin (FMNT) has anticancer properties against breast, prostate and colon cancers. This study aimed to explore the regulatory effect of FMNT/miR-199a-3p/mTOR pathway on Taxol resistance and autophagy in breast cancer (BC). MiR-199a-3p, mTOR, LC3 and other autophagy related proteins were detected in Taxol sensitive and Taxol resistant TNBC cell lines, which were MDA-MB-231 and MDA-MB-231/Taxol, respectively. Cell viability and toxicity were determined by CCK-8 and MTT assay, respectively. The therapeutic effect of FMNT was evaluated in xenotransplantation model of nude mice. MiR-199a-3p was more highly expressed in MDA-MB-231/Taxol than in MDA-MB-231, while mTOR and p-mTOR decreased in MDA-MB-231/Taxol in comparison with MDA-MB-231, and autophagy activation and drug resistance were enhanced. In MDA-MB-231/Taxol cell line, the role of FMNT was verified to inhibit high miR-199a-3p expression. In addition, the combination therapy of FMNT and Taxol was found to be more effective in inhibiting autophagy and drug resistance. Moreover, mTOR was the target of miR-199a-3p, which was confirmed by dual luciferase reporter (DLR) gene assay. Oral administration of FMNT reduced tumor volume after MDA-MB-231/Taxol injection in vivo. Moreover, oral administration of FMNT and Taxol suppressed autophagy and Taxol resistance by restoring mTOR protein level to that of the parent MDA-MB-231, suggesting that miR-199a-3p can severe as a new target to overcome Taxol resistance in TNBC.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7868832 | PMC |
Publication Analysis
Top Keywords
Similar Publications
Harnessing the anticancer potential of Piper nigrum: a synergistic approach to chemotherapy enhancement and reduced side effects.
Discov Oncol
January 2025
Universidad Espíritu Santo, Samborondón, 092301, Ecuador.
Article Synopsis
- Cancer therapy faces issues like drug resistance and severe side effects, prompting exploration of novel, cost-effective treatments like Piper nigrum (black pepper) extract as a complementary anticancer agent.
- Piper nigrum contains bioactive compounds such as piperine that show significant anticancer effects, including tumor inhibition and enhancing the effectiveness of traditional chemotherapy while reducing side effects.
- The review identifies challenges such as variability and bioavailability of PNE, underscoring the need for further research to validate its use in clinical settings and improve cancer treatment outcomes.
Chemotherapy-Induced Cell-Surface GRP78 Expression as a Prognostic Marker for Invasiveness of Metastatic Triple-Negative Breast Cancer.
Ann Biomed Eng
January 2025
Faculty of Biomedical Engineering, Technion-Israel Institute of Technology, 3200003, Haifa, Israel.
Article Synopsis
- Metastasis is responsible for 90% of cancer-related deaths, particularly in triple-negative breast cancer (TNBC), making it essential to understand molecular drivers to find better prognostic markers after chemotherapy.
- Current chemotherapy treatments like doxorubicin and paclitaxel affect tumor cells in various ways, including activating the unfolded protein response (UPR), with GRP78 playing a significant but controversial role in metastasis.
- The study identifies subpopulations of GRP78+ and GRP78- cells in TNBC, demonstrating that while GRP78- cells are more invasive, the combination of both subpopulations may influence overall metastatic potential, offering insights for personalized cancer treatment strategies.
Shared chemoresistance genes in ESCC and cervical Cancer: Insights from pharmacogenomics and Mendelian randomization.
Int Immunopharmacol
January 2025
Department of Pathology, Xiangya Hospital, Central South University, Changsha City, Hunan Province, China; Department of Pathology, School of Basic Medicine, Central South University, Changsha City, Hunan Province, China; Ultrapathology (Biomedical Electron Microscopy) Center, Department of Pathology, Xiang-ya Hospital, Central South University, Changsha City, Hunan Province, China; Key Laboratory of Hunan Province in Neurodegenerative Disorders, Xiangya Hospital, Central South University, Changsha City, Hunan Province, China; National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha City, Hunan Province, China; FuRong Laboratory, Changsha City, Hunan Province, China. Electronic address:
Background: Neoadjuvant chemotherapy, particularly the use of platinum-based compounds and taxanes, is pivotal in the treatment of epithelial-derived tumors, such as cervical cancer and esophageal squamous cell carcinoma (ESCC); however, resistance remains a significant challenge. Utilizing Mendelian randomization (MR) with pharmacogenomics offers a novel approach to understanding the genetic underpinnings of drug responses, thereby aiding in personalized treatment.
Methods: Single-cell RNA sequencing (scRNA-seq) analysis revealed a shared cellular subpopulation of CD8 + T effector memory (CD8 + TEM) cells that are pivotal in mediating chemotherapy resistance in ESCC and cervical cancer.
Unraveling the complexity of HRD assessment in ovarian cancer by combining genomic and functional approaches: translational analyses of MITO16-MaNGO-OV-2 trial.
ESMO Open
January 2025
Uro-Gynecologic Oncology Unit, Istituto Nazionale Tumori IRCCS Fondazione G. Pascale, Naples, Italy. Electronic address:
Background: Ovarian cancer (OvC) constitutes significant management challenges primarily due to its late-stage diagnosis and the development of resistance to chemotherapy. The standard treatment regimen typically includes carboplatin and paclitaxel, with the addition of poly (ADP-ribose) polymerase inhibitors for patients with high-grade serous ovarian cancer (HGSOC) harboring BRCA1/2 mutations. However, the variability in treatment responses suggests the need to investigate factors beyond BRCA1/2 mutations, such as DNA repair mechanisms and epigenetic alterations.
View Article and Find Full Text PDFRecent Prospectives of Cellular Signaling Role for Mammary Gland Carcinogenesis.
Anticancer Agents Med Chem
January 2025
Department of Pharmaceutical Sciences, Lucknow University, Lucknow, UP, India.
In women globally, breast cancer ranks as the second most frequent cause of cancer-related deaths, making up about 25% of female cancer cases, which is pretty standard in affluent countries. Breast cancer is divided into subtypes based on aggressive, genetic and stage. The precise cause of the problem is still unknown.
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!