Exploring the therapeutic potential of “Zhi-Zhen” formula for oxaliplatin resistance in colorectal cancer: an integrated study combining UPLC-QTOF-MS/MS, bioinformatics, network pharmacology, and experimental validation DOI Creative Commons

Yongjing Li,

Ke Chen, Qin Li

et al.

Frontiers in Medicine, Journal Year: 2025, Volume and Issue: 12

Published: Feb. 26, 2025

Chemoresistance is a critical factor compromising the survival of patients with colorectal cancer (CRC). The "Zhi-Zhen" formula (ZZF), traditional prescription developed by Chinese national medicine masters, has been extensively used in clinical practice to treat gastrointestinal cancer. Notably, ZZF potential enhance tumor sensitivity chemotherapy. Although previous vitro studies have demonstrated efficacy overcoming chemoresistance (CRC), its precise molecular mechanisms remain poorly understood. We an integrated approach bioinformatics and network pharmacology predict active ingredients targets alleviating chemoresistance. top five identified degree analysis were validated using mass spectrometry. then established oxaliplatin-resistant CRC cell model explore regulatory through which overcomes at cellular level. Network analyses jointly 29 compounds 13 key ZZF, associated Among these targets, differential expression CASP7 significantly affected progression-free CRC. two lines observed upregulation resistant cells. Furthermore, increases activation cells, promoting apoptosis, thereby ameliorating Additionally, β-catenin knockdown led expression, whereas Wnt/β-catenin signaling pathway reduced protein levels. decreases activity decreasing transcription nuclear localization. value treatment inhibiting localization β-catenin, increasing enhancing apoptotic response chemoresistant

Language: Английский

Wnt/β-catenin signaling pathway in carcinogenesis and cancer therapy DOI Creative Commons

Pan Song,

Zirui Gao, Yige Bao

et al.

Journal of Hematology & Oncology, Journal Year: 2024, Volume and Issue: 17(1)

Published: June 18, 2024

Abstract The Wnt/β-catenin signaling pathway plays a crucial role in various physiological processes, encompassing development, tissue homeostasis, and cell proliferation. Under normal conditions, the is meticulously regulated. However, aberrant activation of this downstream target genes can occur due to mutations key components pathway, epigenetic modifications, crosstalk with other pathways. Consequently, these dysregulations contribute significantly tumor initiation progression. Therapies targeting transduction have exhibited promising prospects potential for treatment. An increasing number medications are continuously being developed validated. This comprehensive review aims summarize latest advances our understanding played by carcinogenesis targeted therapy, providing valuable insights into acknowledging current opportunities challenges associated cancer research

Language: Английский

Citations

76
Wnt/β-Catenin signaling pathway in hepatocellular carcinoma: pathogenic role and therapeutic target DOI Creative Commons

Zekun Zhao,

Tenglu Cui,

Fengxian Wei

et al.

Frontiers in Oncology, Journal Year: 2024, Volume and Issue: 14

Published: April 2, 2024

Hepatocellular carcinoma (HCC) is the most common primary malignant liver tumor and one of leading causes cancer-related deaths worldwide. The Wnt/β-Catenin signaling pathway a highly conserved involved in several biological processes, including improper regulation that leads to tumorigenesis progression cancer. New studies have found abnormal activation major cause HCC tumorigenesis, progression, resistance therapy. perspectives approaches treating will arise from understanding this pathway. This article offers thorough analysis pathway’s function its therapeutic implications HCC.

Language: Английский

Citations

15
Fusobacterium nucleatum modulates the Wnt/β-catenin pathway in colorectal cancer development DOI
Tanushree Mondal, Deepanjan Chattopadhyay, P. Mondal

et al.

International Journal of Biological Macromolecules, Journal Year: 2025, Volume and Issue: 299, P. 140196 - 140196

Published: Jan. 21, 2025

Language: Английский

Citations

2
The Impact of Cancer Stem Cells in Colorectal Cancer DOI Open Access
Petru Radu, Mihai Zurzu, Anca Tigora

et al.

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(8), P. 4140 - 4140

Published: April 9, 2024

Despite incessant research, colorectal cancer (CRC) is still one of the most common causes fatality in both men and women worldwide. Over time, advancements medical treatments have notably enhanced survival rates patients with cancer. Managing metastatic CRC involves a complex tradeoff between potential benefits adverse effects treatment, considering factors like disease progression, treatment toxicity, drug resistance, overall impact on patient's quality life. An increasing body evidence highlights significance stem cell (CSC) concept, proposing that CSCs occupy central role triggering been focal point extensive research variety types, including CRC. Colorectal cells (CCSCs) play crucial tumor initiation, metastasis, therapy making them targets. Various methods exist for isolating CCSCs, understanding mechanisms resistance associated crucial. This paper offers an overview current pertaining to comprehension

Language: Английский

Citations

9
Pharmacophore-based identification and in Silico characterization of microbial metabolites as potential modulators of Wnt signaling pathway in colorectal cancer therapy DOI

Divya Sharma,

Sivakumar Arumugam

Molecular Diversity, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 8, 2025

Language: Английский

Citations

1
Unveiling the future of cancer stem cell therapy: a narrative exploration of emerging innovations DOI Creative Commons

Joseph Nhyira Obisi,

Abike Ndidiamaka Josephine Abimbola,

Oluwasegun Adesina Babaleye

et al.

Discover Oncology, Journal Year: 2025, Volume and Issue: 16(1)

Published: March 22, 2025

Cancer stem cells (CSCs), are a critical subpopulation within tumours, and defined by their capacity for self-renewal, differentiation, tumour initiation. These unique traits contribute to progression, metastasis, resistance conventional treatments like chemotherapy radiotherapy, often resulting in cancer recurrence poor patient outcomes. As such, CSCs have become focal points developing advanced therapies. This review highlights progress CSC-targeted treatments, including chimeric antigen receptor T-cell (CAR-T) therapy, immunotherapy, molecular targeting, nanoparticle-based drug delivery systems. Plant-derived compounds gene-editing technologies, such as clustered regularly interspaced short palindromic repeats (CRISPR), explored potential enhance precision minimize side effects. Metabolic pathways integral CSC survival, mitochondrial dynamics, mitophagy (regulated dynamin-related protein 1 [DRP1] the PINK1/Parkin pathway), one-carbon metabolism, amino acid metabolism (involving enzymes glutaminase (GLS) glutamate dehydrogenase (GDH]), lipid hypoxia-induced metabolic reprogramming mediated hypoxia-inducible factors (HIF-1α HIF-2α), examined therapeutic targets. The adaptability of through autophagy, flexibility, epigenetic regulation metabolites α-ketoglutarate, succinate, fumarate is discussed. Additionally, extracellular vesicles nicotinamide adenine dinucleotide (NAD⁺) identified pivotal redox balance, DNA repair, modifications. Addressing challenges heterogeneity, immune evasion, treatment durability requires interdisciplinary collaboration. Advancing therapies essential overcoming preventing relapse, paving way transformative treatments. underscores importance leveraging innovative technologies fostering collaboration revolutionize treatment.

Language: Английский

Citations

1
The Role of Cancer Stem Cell Markers in Ovarian Cancer DOI Open Access
Karolina Frąszczak, Bartłomiej Barczyński

Cancers, Journal Year: 2023, Volume and Issue: 16(1), P. 40 - 40

Published: Dec. 20, 2023

Ovarian cancer is the most lethal gynaecological and eighth common female cancer. The early diagnosis of ovarian remains a clinical problem despite significant development technology. Nearly 70% patients with are diagnosed stages III–IV metastatic disease. Reliable diagnostic prognostic biomarkers currently lacking. recurrence resistance to chemotherapy pose vital problems translate into poor outcomes. Cancer stem cells appear be responsible for tumour resulting from chemotherapeutic resistance. These also crucial initiation due ability self-renew, differentiate, avoid immune destruction, promote inflammation angiogenesis. Studies have confirmed an association between CSC occurrence chemotherapy, subsequent metastases, relapses. Therefore, elimination CSCs appears important overcoming drug improving prognoses. This review focuses on expression selected markers, including CD133, CD44, CD24, CD117, aldehyde dehydrogenase 1, which show potential significance. Some markers expressed surface correlate features can used prognosis However, heterogeneity plasticity CSCs, determination specific phenotypes difficult.

Language: Английский

Citations

14
Role of Wnt/β-catenin pathway in cancer drug resistance: Insights into molecular aspects of major solid tumors DOI
Charudatt Samant, Ramesh R. Kale, K. Sreedhara Ranganath Pai

et al.

Biochemical and Biophysical Research Communications, Journal Year: 2024, Volume and Issue: 729, P. 150348 - 150348

Published: July 4, 2024

Language: Английский

Citations

6
Unlocking Hope: Therapeutic Advances and Approaches in Modulating the Wnt Pathway for Neurodegenerative Diseases DOI Creative Commons

Navid Faraji,

Negar Ebadpour, Mohammad Abavisani

et al.

Molecular Neurobiology, Journal Year: 2024, Volume and Issue: unknown

Published: Sept. 23, 2024

Language: Английский

Citations

6
Modified Lichong decoction intervenes in colorectal cancer by modulating the intestinal flora and the Wnt/β-catenin signaling pathway DOI Creative Commons
Longhui Liu,

Mengmeng Zhao,

Xiaomeng Lang

et al.

Journal of Cancer Research and Clinical Oncology, Journal Year: 2024, Volume and Issue: 150(5)

Published: May 6, 2024

Abstract Background The pathogenesis and treatment of colorectal cancer (CRC) continue to be areas ongoing research, especially the benefits traditional Chinese medicine (TCM) in slowing progression CRC. This study was conducted investigate effectiveness mechanism action modified Lichong decoction (MLCD) inhibiting CRC progression. Methods We established animal models using azoxymethane/dextran sodium sulfate (AOM/DSS) administered high, medium, or low doses MLCD mesalazine (MS) for 9 weeks observe alleviation optimal dose group then subjected metagenomic RNA sequencing (RNA-seq) explore differentially abundant flora genes control, model groups. Finally, verified WB, qRT‒PCR, immunohistochemistry TUNEL staining. Results inhibited CRC, effect observed at high doses. regulated structure function intestinal by decreasing abundance harmful bacteria increasing that beneficial bacteria. expressed were mainly associated with Wnt/β-catenin pathway cell cycle. Molecular biology analysis indicated suppressed epithelial–mesenchymal transition (EMT), abnormal proliferation promoted epithelial apoptosis. Conclusion mitigated growth cells apoptosis, thereby inhibition accomplished modifying microbiota disrupting EMT. Therefore, could serve as a potential component TCM prescriptions treatment.

Language: Английский

Citations

5