NAD+/SIRT1 pathway regulates glycolysis to promote oxaliplatin resistance in colorectal cancer DOI

Yaru Niu,

Michael Xiang, Wenwei Yang

и другие.

World Journal of Gastroenterology, Год журнала: 2025, Номер 31(11)

Опубликована: Март 12, 2025

BACKGROUND Glycolysis provides growth advantages and leads to drug resistance in colorectal cancer (CRC) cells. SIRT1, an NAD+-dependent deacetylase, regulates various cellular processes, its upregulation results antitumor effects. This study investigated the role of SIRT1 metabolic reprogramming oxaliplatin CRC AIM To investigate overcoming METHODS We performed transcriptome sequencing human parental cells oxaliplatin-resistant identify differentially expressed genes. Key regulators were identified via LINCS database. NAD+ levels measured by flow cytometry, effects on sensitivity assessed MTS assays, colony formation xenograft models. Glycolytic function was using Western blot Seahorse assays. RESULTS Salermide, a inhibitor, as candidate compound that enhances resistance. In cells, downregulated, whereas γH2AX PARP upregulated. activation led depletion inhibition, which reversed inhibitor treatment. The increase expression overcame resistance, while inhibition increased glycolysis, inhibited glycolysis resistant characterized reduced glycolytic enzymes PKM2 LDHA, well decreased extracellular acidification rate. shikonin induced inhibition. CONCLUSION is due activation, turn increases glycolysis. Restoring reverses offering promising therapeutic strategy overcome

Язык: Английский

Unveiling the mechanisms and challenges of cancer drug resistance DOI Creative Commons
Sameer Ullah Khan, Kaneez Fatima,

Shariqa Aisha

и другие.

Cell Communication and Signaling, Год журнала: 2024, Номер 22(1)

Опубликована: Фев. 12, 2024

Abstract Cancer treatment faces many hurdles and resistance is one among them. Anti-cancer strategies are evolving due to innate acquired capacity, governed by genetic, epigenetic, proteomic, metabolic, or microenvironmental cues that ultimately enable selected cancer cells survive progress under unfavorable conditions. Although the mechanism of drug being widely studied generate new target-based drugs with better potency than existing ones. However, broader flexibility in resistance, advanced therapeutic options efficacy need be explored. Combination therapy an alternative a success rate though risk amplified side effects commonplace. Moreover, recent groundbreaking precision immune ways overcome has revolutionized anticancer greater extent only limitation individual-specific needs further attention. This review will focus on challenges opted withstand current therapies at molecular level also highlights emerging -like immunological, stem cell-based may prove have potential challenge problem resistance.

Язык: Английский

Процитировано

107

Chemical Design of Magnetic Nanomaterials for Imaging and Ferroptosis-Based Cancer Therapy DOI

Wei Xu,

Guoqiang Guan, Renye Yue

и другие.

Chemical Reviews, Год журнала: 2025, Номер unknown

Опубликована: Фев. 14, 2025

Ferroptosis, an iron-dependent form of regulatory cell death, has garnered significant interest as a therapeutic target in cancer treatment due to its distinct characteristics, including lipid peroxide generation and redox imbalance. However, clinical application oncology is currently limited by issues such suboptimal efficacy potential off-target effects. The advent nanotechnology provided new way for overcoming these challenges through the development activatable magnetic nanoparticles (MNPs). These innovative MNPs are designed improve specificity ferroptosis induction. This Review delves into chemical biological principles guiding design ferroptosis-based therapies imaging-guided therapies. It discusses mechanisms attributes ferroptosis, composition MNPs, their mechanism action inducers, integration with advanced imaging techniques monitoring. Additionally, we examine convergence other strategies, chemodynamic therapy, photothermal photodynamic sonodynamic immunotherapy, within context nanomedicine strategies utilizing MNPs. highlights multifunctional surpass limitations conventional treatments, envisioning future drug-resistance-free, precision diagnostics treating recalcitrant cancers.

Язык: Английский

Процитировано

7

Doxorubicin-loaded micelles in tumor cell-specific chemotherapy DOI
Yasir Qasim Almajidi, Mustafa M. Kadhim,

Fahad Alsaikhan

и другие.

Environmental Research, Год журнала: 2023, Номер 227, С. 115722 - 115722

Опубликована: Март 21, 2023

Язык: Английский

Процитировано

42

Nrf2 inhibition increases sensitivity to chemotherapy of colorectal cancer by promoting ferroptosis and pyroptosis DOI Creative Commons

Yongzhou Huang,

Wenchang Yang, Lei Yang

и другие.

Scientific Reports, Год журнала: 2023, Номер 13(1)

Опубликована: Сен. 1, 2023

Abstract Oxaliplatin is widely used in chemotherapy for colorectal cancer (CRC), but its sensitivity has become a major obstacle to limiting efficacy. Many literatures reported that Nrf2 activation promoted tumor chemoresistance. In this study, we explored the role and mechanism of inhibition oxaliplatin-based chemosensitivity CRC. vitro experiments, applied 4-octyl itaconate (4-OI) activate Nrf2, lentivirus knock down CRC cell lines. By measuring viability, colony formation, apoptosis, reactive oxygen species production, western blot, found oxaliplatin lobaplatin suppressed growth HCT-116 LOVO cells dose-dependent manner, expression Nrf2. 4-OI, an activator, reduced sensibility lobaplatin, while knockdown lobaplatin. Through public databases, GPX4 normal tissues was lower compared with CRC, high predicted poor prognosis. Meanwhile, vitro. The enhanced effects reduce GSH content, increase MDA which oxaliplatin-induced ferroptosis. Subsequently, GSDME-N, induced LDH, IL-1β, TNF-a release, aggravated occurrence GSMDE-mediated pyroptosis. Finally, on HCT116 xenograft vivo. Thus, our study showed improved by promoting ferroptosis pyroptosis, provided new target overcoming chemoresistance

Язык: Английский

Процитировано

35

Cancer-associated fibroblasts undergoing neoadjuvant chemotherapy suppress rectal cancer revealed by single-cell and spatial transcriptomics DOI Creative Commons
Pengfei Qin, Huaxian Chen, Yuhang Wang

и другие.

Cell Reports Medicine, Год журнала: 2023, Номер 4(10), С. 101231 - 101231

Опубликована: Окт. 1, 2023

Neoadjuvant chemotherapy (NAC) for rectal cancer (RC) shows promising clinical response. The modulation of the tumor microenvironment (TME) by NAC and its association with therapeutic response remain unclear. Here, we use single-cell RNA sequencing spatial transcriptome to examine cell dynamics in 29 patients RC, who are sampled pairwise before after treatment. We construct a high-resolution cellular dynamic landscape remodeled their associations markedly reshapes populations cancer-associated fibroblasts (CAFs), which is strongly associated CAF subsets regulate TME through recruitment crosstalk activate immunity suppress progression multiple cytokines, including CXCL12, SLIT2, DCN. In contrast, epithelial-mesenchymal transition malignant cells upregulated CAF_FAP MIR4435-2HG induction, resulting worse outcomes. Our study demonstrates that inhibits modulates remodeling CAFs.

Язык: Английский

Процитировано

30

Theranostics Nanomedicine Applications for Colorectal Cancer and Metastasis: Recent Advances DOI Open Access

Phanindra Babu Kasi,

Venkata Ramana Mallela, Filip Ambrożkiewicz

и другие.

International Journal of Molecular Sciences, Год журнала: 2023, Номер 24(9), С. 7922 - 7922

Опубликована: Апрель 27, 2023

Colorectal cancer (CRC) is the third most common worldwide, and metastatic CRC a fatal disease. The CRC-affected tissues show several molecular markers that could be used as fresh strategy to create newer methods of treating condition. liver peritoneum are where metastasis occurs frequently. Once tumor has metastasized liver, peritoneal carcinomatosis frequently regarded disease's final stage. However, nearly 50% patients with do not have metastases. New diagnostic therapeutic approaches must developed due poor response present treatment choices in advanced stages necessity an accurate diagnosis early stages. Many unique amazing nanomaterials promise for both may found nanotechnology. Numerous nanoformulations, including carbon nanotubes, dendrimers, liposomes, silica nanoparticles, gold metal-organic frameworks, core-shell polymeric nano-formulations, nano-emulsion systems, among others, can targeted anticancer drug delivery purposes CRC. Theranostic combined nanomedicine been proposed revolutionary approach improve detection treatment. This review highlights recent studies, potential, challenges development nanoplatforms

Язык: Английский

Процитировано

26

STAT3 as a newly emerging target in colorectal cancer therapy: Tumorigenesis, therapy response, and pharmacological/nanoplatform strategies DOI
Mehrdad Hashemi,

Sahar Abbaszadeh,

Mohsen Rashidi

и другие.

Environmental Research, Год журнала: 2023, Номер 233, С. 116458 - 116458

Опубликована: Июнь 21, 2023

Язык: Английский

Процитировано

24

The expression of exosomal and cellular miRNAs in predicting oxaliplatin resistance in colorectal cancer cells: an in silico and in vitro study DOI Creative Commons

Hoda Deli,

Zeynab Vakili-Ghartavol,

Yazdan Asgari

и другие.

BMC Cancer, Год журнала: 2025, Номер 25(1)

Опубликована: Янв. 9, 2025

Colorectal cancer (CRC) is a common gastrointestinal cancer, and even though oxaliplatin chemotherapy effective, there high likelihood of relapse, indicating the presence oxaliplatin-resistant CRC. Therefore, it crucial to comprehend molecular mechanisms resistance develop effective strategies counter drug resistance. Numerous studies have demonstrated close association between microRNAs (miRNAs) in In this study, we aimed identify essential exosomal cellular miRNA related CRC cell line HCT-116. The expression profile cells with was analyzed. effectiveness diagnostics biomarker potency miRNAs were evaluated by receiver operating characteristic (ROC) analysis. Target identified, enrichment analysis assessed based on Gene Ontology (GO), Reactome, Human Disease (DO). vitro experiments, HCT-116 (HCT116-OXA) developed, exosomes isolated characterized from HCT116-OXA HCT116 cells. selected their exosomes, they compared using quantitative real-time PCR. This study revealed that combination miR-4326, miR-3615, miR-7974, miR-130b-3p, miR-454-3p exhibited highest area under curve (AUC), sensitivity, specificity, superior diagnostic predictive performance. displayed reduced early late apoptosis, bypass S phase arrest, prolonged doubling time, higher IC50 parental miR-454-3p, miR-4326 decreased as sensitive However, significantly miR-130b-3p observed low miR-3615 or could predict response therapy. indicates potential these specific serve markers for

Язык: Английский

Процитировано

2

miRNA-sequencing and bioinformatics analyses of key miRNAs and their associated genes regulated by EC-synthetic retinoids treatment in Caco-2 cancer cells DOI
Hesham Haffez, Ahmed M. Sayed

Gene Reports, Год журнала: 2025, Номер unknown, С. 102145 - 102145

Опубликована: Янв. 1, 2025

Язык: Английский

Процитировано

1

Amphiphilic polymeric nanodrug integrated with superparamagnetic iron oxide nanoparticles for synergistic antibacterial and antitumor therapy of colorectal cancer DOI Open Access
Xiaohui Li,

Jiazhen Niu,

Lingling Deng

и другие.

Acta Biomaterialia, Год журнала: 2023, Номер 173, С. 432 - 441

Опубликована: Ноя. 19, 2023

Язык: Английский

Процитировано

19