PDF(Pubmed)
Abstract：
BACKGROUND: Breast cancer is a serious threat to women\'s health with high morbidity and mortality. The development of more effective therapies for the treatment of breast cancer is strongly warranted. Growing evidence suggests that targeting glucose metabolism may be a promising cancer treatment strategy. We previously identified a new glyceraldehyde-3-phosphate dehydrogenase (GAPDH) inhibitor, DC-5163, which shows great potential in inhibiting tumor growth. Here, we evaluated the anticancer potential of DC-5163 in breast cancer cells.
METHODS: The effects of DC-5163 on breast cancer cells were investigated in vitro and in vivo. Seahorse, glucose uptake, lactate production, and cellular ATP content assays were performed to examine the impact of DC-5163 on cellular glycolysis. Cell viability, colony-forming ability, cell cycle, and apoptosis were assessed by CCK8 assay, colony formation assay, flow cytometry, and immunoblotting respectively. The anticancer activity of DC-5163 in vivo was evaluated in a mouse breast cancer xenograft model.
RESULTS: DC-5163 suppressed aerobic glycolysis and reduced energy supply of breast cancer cells, thereby inhibiting breast cancer cell growth, inducing cell cycle arrest in the G0/G1 phase, and increasing apoptosis. The therapeutic efficacy was assessed using a breast cancer xenograft mouse model. DC-5163 treatment markedly suppressed tumor growth in vivo without inducing evident systemic toxicity. Micro-PET/CT scans revealed a notable reduction in tumor 18F-FDG and 18F-FLT uptake in the DC-5163 treatment group compared to the DMSO control group.
CONCLUSIONS: Our results suggest that DC-5163 is a promising GAPDH inhibitor for suppressing breast cancer growth without obvious side effects. 18F-FDG and 18F-FLT PET/CT can noninvasively assess the levels of glycolysis and proliferation in tumors following treatment with DC-5163.
METHODS: The effects of DC-5163 on breast cancer cells were investigated in vitro and in vivo. Seahorse, glucose uptake, lactate production, and cellular ATP content assays were performed to examine the impact of DC-5163 on cellular glycolysis. Cell viability, colony-forming ability, cell cycle, and apoptosis were assessed by CCK8 assay, colony formation assay, flow cytometry, and immunoblotting respectively. The anticancer activity of DC-5163 in vivo was evaluated in a mouse breast cancer xenograft model.
RESULTS: DC-5163 suppressed aerobic glycolysis and reduced energy supply of breast cancer cells, thereby inhibiting breast cancer cell growth, inducing cell cycle arrest in the G0/G1 phase, and increasing apoptosis. The therapeutic efficacy was assessed using a breast cancer xenograft mouse model. DC-5163 treatment markedly suppressed tumor growth in vivo without inducing evident systemic toxicity. Micro-PET/CT scans revealed a notable reduction in tumor 18F-FDG and 18F-FLT uptake in the DC-5163 treatment group compared to the DMSO control group.
CONCLUSIONS: Our results suggest that DC-5163 is a promising GAPDH inhibitor for suppressing breast cancer growth without obvious side effects. 18F-FDG and 18F-FLT PET/CT can noninvasively assess the levels of glycolysis and proliferation in tumors following treatment with DC-5163.
摘要：
背景：乳腺癌是妇女健康的严重威胁，发病率和死亡率都很高。迫切需要开发更有效的治疗乳腺癌的疗法。越来越多的证据表明，靶向葡萄糖代谢可能是一种有前途的癌症治疗策略。我们先前鉴定了一种新的甘油醛-3-磷酸脱氢酶（GAPDH）抑制剂，DC-5163在抑制肿瘤生长方面显示出巨大潜力。这里,我们评估了DC-5163在乳腺癌细胞中的抗癌潜力。
方法：体外和体内研究了DC-5163对乳腺癌细胞的作用。海马,葡萄糖摄取，乳酸生产，进行细胞ATP含量测定以检查DC-5163对细胞糖酵解的影响。细胞活力，菌落形成能力，细胞周期,和细胞凋亡通过CCK8测定进行评估，集落形成试验,流式细胞术,和免疫印迹。在小鼠乳腺癌异种移植模型中评估DC-5163的体内抗癌活性。
结果：DC-5163抑制有氧糖酵解并减少乳腺癌细胞的能量供应，从而抑制乳腺癌细胞的生长，诱导细胞周期停滞在G0/G1期，增加细胞凋亡。使用乳腺癌异种移植小鼠模型评估治疗功效。DC-5163治疗在体内显著抑制肿瘤生长而不诱导明显的全身毒性。Micro-PET/CT扫描显示,与DMSO对照组相比,DC-5163治疗组的肿瘤18F-FDG和18F-FLT摄取显著减少。
结论：我们的结果表明，DC-5163是一种有前途的GAPDH抑制剂，用于抑制乳腺癌的生长，而没有明显的副作用。18F-FDG和18F-FLTPET/CT可以无创评估DC-5163治疗后肿瘤的糖酵解和增殖水平。
方法：体外和体内研究了DC-5163对乳腺癌细胞的作用。海马,葡萄糖摄取，乳酸生产，进行细胞ATP含量测定以检查DC-5163对细胞糖酵解的影响。细胞活力，菌落形成能力，细胞周期,和细胞凋亡通过CCK8测定进行评估，集落形成试验,流式细胞术,和免疫印迹。在小鼠乳腺癌异种移植模型中评估DC-5163的体内抗癌活性。
结果：DC-5163抑制有氧糖酵解并减少乳腺癌细胞的能量供应，从而抑制乳腺癌细胞的生长，诱导细胞周期停滞在G0/G1期，增加细胞凋亡。使用乳腺癌异种移植小鼠模型评估治疗功效。DC-5163治疗在体内显著抑制肿瘤生长而不诱导明显的全身毒性。Micro-PET/CT扫描显示,与DMSO对照组相比,DC-5163治疗组的肿瘤18F-FDG和18F-FLT摄取显著减少。
结论：我们的结果表明，DC-5163是一种有前途的GAPDH抑制剂，用于抑制乳腺癌的生长，而没有明显的副作用。18F-FDG和18F-FLTPET/CT可以无创评估DC-5163治疗后肿瘤的糖酵解和增殖水平。
