ArticleOncology letters2020
Efficacy and mechanism of combination of oxaliplatin with PKM2 knockdown in colorectal cancer.
Article in Oncology letters, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed.
- Targeting Pyruvate Kinase M2: Signal Transduction Pathways and Exploration of Cancer Therapeutic Strategies.The AAPS journal · 2026Review
- Glucose Metabolic Reprogramming in Colorectal Cancer: From Mechanisms to Targeted Therapy Approaches.Cancer medicine · 2025Review
- Article
- Assessment of Cell Viability in Drug Therapy: IC50 and Other New Time-Independent Indices for Evaluating Chemotherapy Efficacy.Pharmaceutics · 2025Article
- In vivo antibody library screening identifies PKM2-targeting M1 antibody with antitumor activity in melanoma.American journal of cancer research · 2025Article
- Targeting PKM2 in cancer therapeutics: mechanistic advances and translational opportunities.Frontiers in immunology · 2025Review
- Role of glucose metabolic reprogramming in colorectal cancer progression and drug resistance.Translational oncology · 2024Review
- Pyruvate kinase M2 (PKM-2) expression and prognostic significance in glioblastoma patients.Journal of neuro-oncology · 2023Article
- Aspirin reprogrammes colorectal cancer cell metabolism and sensitises to glutaminase inhibition.Cancer & metabolism · 2023Article
- Monitoring Metabolic Changes in Response to Chemotherapies in Cancer with Raman Spectroscopy and Metabolomics.Analytical chemistry · 2023Article
- The Crosstalk and Clinical Implications of CircRNAs and Glucose Metabolism in Gastrointestinal Cancers.Cancers · 2023Review
- Role of AMPK in Regulation of Oxaliplatin-Resistant Human Colorectal Cancer.Biomedicines · 2022Article
- The Role of PKM2 in the Regulation of Mitochondrial Function: Focus on Mitochondrial Metabolism, Oxidative Stress, Dynamic, and Apoptosis. PKM2 in Mitochondrial Function.Oxidative medicine and cellular longevity · 2022Review
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Authors and funding
7 authors.
Funding
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Abstract
M2 isomer of pyruvate kinase (PKM2), a key enzyme in aerobic glycolysis, is closely related to cancer development and progression. Suppression of PKM2 exhibits synergistic effects with docetaxel in lung cancer, but the therapeutic potential in colorectal cancer (CRC) is unclear. The aim of the present study was to explore the synergic effects and mechanism of knocking down PKM2 combined with oxaliplatin (a chemosensitizer) treatment in two CRC cell lines (HCT116 and DLD1). The PKM2 gene was initially knocked down using small interfering (si)RNAs (si155 and si156). Subsequently, the effects of PKM2-siRNAs and oxaliplatin, on CRC cells were determined using MTS, cell cycle analysis and apoptosis assays. The mechanism of targeting PKM2 was explored by detecting glucose uptake, lactate secretion fluxes, and the levels of glucose-6-phosphate dehydrogenase (G6PD) mRNA, glutathione (GSH) and reactive oxygen species (ROS). Cell viability in the experimental groups (PKM2-siRNAs, oxaliplatin, PKM2-siRNAs + oxaliplatin) was significantly reduced compared with the control group, and combination treatments (PKM2-siRNAs + oxaliplatin) were more effective than single treatments (PKM2-siRNAs and oxaliplatin only groups). Similar results were observed with the apoptosis assay. The combination groups showed synergistic effects compared with both single treatment groups. Furthermore, glucose uptake and lactate secretion and mRNA levels of G6PD and PKM2 were decreased after PKM2 knockdown in the PKM2-siRNAs and PKM2-siRNAs + oxaliplatin groups. The GSH levels in the PKM2-siRNAs group was significantly lower compared with the negative control group. The ROS levels in the PKM2-siRNAs groups were also significantly increased. The combination of PKM2-siRNAs and oxaliplatin had synergistic effects on CRC cells (HCT116 and DLD1). PKM2 silencing may alter energy metabolism in cancer cells and initiate ROS-induced apoptosis after downregulation of the pentose phosphate pathway by PKM2-siRNAs.
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