Hagyousif Yousra A, Zenati Ruba A, Soares Nelson C, Al-Hroub Hamza M, Khan Farman Matloob, Qaisar Rizwan, Hamoudi Rifat, El-Awady Raafat, Abuhelwa Ahmad Y, Ramadan Wafaa, El-Huneidi Waseem, Abu-Gharbieh Eman, Alzoubi Karem H, Bustanji Yasser, Semreen Mohammad H
Research Institute for Medical and Health Sciences, University of Sharjah, Sharjah, United Arab Emirates.
College of Pharmacy, Department of Medicinal Chemistry, University of Sharjah, United Arab Emirates.
Toxicol Rep. 2025 May 14;14:102045. doi: 10.1016/j.toxrep.2025.102045. eCollection 2025 Jun.
Colorectal cancer (CRC) is one of the most common cancers worldwide, yet it continues to have a low survival rate, largely due to the lack of effective treatments. Metabolomics offers new insight into disease diagnosis and biomarkers discovery. The aim of the study is to identify serum biomarkers in a CRC xenograft mouse model treated with topotecan using advanced metabolomics techniques to enhance our understanding and management of the disease.
The therapeutic potentials of the anticancer drug topotecan on metabolomic alterations in CRC were explored using the UHPLC-ESI-QTOF-MS platform. A comprehensive metabolomic analysis was conducted to compare four different animal groups: HCT-116 CRC xenograft mice treated with topotecan (treated group), vehicle-control HCT-116 xenograft mice (untreated CRC xenograft mice), positive controls (healthy mice injected with topotecan), and negative controls (healthy mice).
The study identified 53 altered metabolites across all four groups ( < 0.05). Independent T-test revealed that 15 metabolites were statistically significant among vehicle controls and negative controls. Additionally, 20 metabolites showed significant differences between the potential responders to topotecan and the vehicle controls. Moreover, only one metabolite was statistically significant between the positive and negative controls.
The findings provide a detailed characterization of metabolic alterations associated with topotecan treatment in CRC. These insights contribute to a better understanding of the drug's mechanism of action, which may help predict CRC patients' response to topotecan and guide the development of personalized therapeutic strategies.
结直肠癌（CRC）是全球最常见的癌症之一，但其生存率仍然较低，这在很大程度上是由于缺乏有效的治疗方法。代谢组学为疾病诊断和生物标志物发现提供了新的见解。本研究的目的是使用先进的代谢组学技术，在接受拓扑替康治疗的CRC异种移植小鼠模型中鉴定血清生物标志物，以加强我们对该疾病的理解和管理。
使用UHPLC-ESI-QTOF-MS平台探索抗癌药物拓扑替康对CRC代谢组学改变的治疗潜力。进行了全面的代谢组学分析，以比较四个不同的动物组：接受拓扑替康治疗的HCT-116 CRC异种移植小鼠（治疗组）、载体对照HCT-116异种移植小鼠（未治疗的CRC异种移植小鼠）、阳性对照（注射拓扑替康的健康小鼠）和阴性对照（健康小鼠）。
该研究在所有四组中鉴定出53种改变的代谢物（<0.05）。独立T检验显示，在载体对照和阴性对照中有15种代谢物具有统计学意义。此外，20种代谢物在拓扑替康潜在反应者和载体对照之间显示出显著差异。此外，阳性和阴性对照之间只有一种代谢物具有统计学意义。
这些发现详细描述了与CRC中拓扑替康治疗相关的代谢改变。这些见解有助于更好地理解药物的作用机制，这可能有助于预测CRC患者对拓扑替康的反应，并指导个性化治疗策略的制定。
