Moutabian Hossein, Majdaeen Mehrsa, Ghahramani-Asl Ruhollah, Yadollahi Masoumeh, Gharepapagh Esmaeil, Ataei Gholamreza, Falahatpour Zahra, Bagheri Hamed, Farhood Bagher
Radiation Sciences Research Center (RSRC), AJA University of Medical Sciences, Tehran, Iran.
Department of Radiotherapy and Oncology, Razi Hospital, Guilan University of Medical Sciences, Rasht, Iran.
Cancer Cell Int. 2022 Apr 2;22(1):142. doi: 10.1186/s12935-022-02561-7.
5-fluorouracil (5-FU), an effective chemotherapy drug, is commonly applied for colorectal cancer treatment. Nevertheless, its toxicity to normal tissues and the development of tumor resistance are the main obstacles to successful cancer chemotherapy and hence, its clinical application is limited. The use of resveratrol can increase 5-FU-induced cytotoxicity and mitigate the unwanted adverse effects. This study aimed to review the potential therapeutic effects of resveratrol in combination with 5-FU against colorectal cancer.
According to the PRISMA guideline, a comprehensive systematic search was carried out for the identification of relevant literature in four electronic databases of PubMed, Web of Science, Embase, and Scopus up to May 2021 using a pre-defined set of keywords in their titles and abstracts. We screened 282 studies in accordance with our inclusion and exclusion criteria. Thirteen articles were finally included in this systematic review.
The in vitro findings showed that proliferation inhibition of colorectal cancer cells in the groups treated by 5-FU was remarkably higher than the untreated groups and the co-administration of resveratrol remarkably increased cytotoxicity induced by 5-FU. The in vivo results demonstrated a decrease in tumor growth of mice treated by 5-FU than the untreated group and a dramatic decrease was observed following combined treatment of resveratrol and 5-FU. It was also found that 5-FU alone and combined with resveratrol could regulate the cell cycle profile of colorectal cancer cells. Moreover, this chemotherapeutic agent induced the biochemical and histopathological changes in the cancerous cells/tissues and these alterations were synergized by resveratrol co-administration (for most of the cases), except for the inflammatory mediators.
The results obtained from this systematic review demonstrated that co-administration of resveratrol could sensitize the colorectal cancer cells to 5-FU treatment via various mechanisms, including regulation of cell cycle distribution, oxidant, apoptosis, anti-inflammatory effects.
5-氟尿嘧啶（5-FU）是一种有效的化疗药物，常用于结直肠癌的治疗。然而，其对正常组织的毒性以及肿瘤耐药性的产生是癌症化疗成功的主要障碍，因此其临床应用受到限制。白藜芦醇的使用可以增加5-FU诱导的细胞毒性，并减轻不良副作用。本研究旨在综述白藜芦醇联合5-FU对结直肠癌的潜在治疗效果。
根据PRISMA指南，在截至2021年5月的PubMed、Web of Science、Embase和Scopus这四个电子数据库中，使用预先定义的关键词集在标题和摘要中进行全面系统的检索，以确定相关文献。我们根据纳入和排除标准筛选了282项研究。最终有13篇文章被纳入本系统评价。
体外研究结果表明，5-FU处理组对结直肠癌细胞的增殖抑制作用明显高于未处理组，白藜芦醇的共同给药显著增加了5-FU诱导的细胞毒性。体内结果显示，5-FU处理的小鼠肿瘤生长比未处理组有所减少，白藜芦醇与5-FU联合治疗后肿瘤生长显著减少。还发现，单独使用5-FU以及与白藜芦醇联合使用均可调节结直肠癌细胞的细胞周期分布。此外，这种化疗药物诱导癌细胞/组织发生生化和组织病理学变化，除炎症介质外，这些变化在白藜芦醇共同给药时（大多数情况下）具有协同作用。
本系统评价的结果表明，白藜芦醇的共同给药可通过多种机制使结直肠癌细胞对5-FU治疗敏感，包括调节细胞周期分布、氧化、凋亡、抗炎作用。
