结直肠癌进展与抑制的十字路口:间充质干细胞治疗干预效果及难题

Crossroads of colorectal cancer progression and suppression:efficacy and challenges of mesenchymal stem cell therapy interventions

背景:结直肠癌早期的治疗方法包括内镜和手术切除,但是术后并发症多,晚期多采用化疗方法,然而化疗会引起胃肠功能紊乱、骨髓抑制、肝肾功能损伤等不良反应,导致大多数患者不主动、不配合治疗。目的:综述间充质干细胞治疗结直肠癌的作用机制、最新治疗进展及目前存在的问题,为将来临床应用提供依据。方法:计算机检索Pub Med数据库、中国知网、万方数据库收录的相关文献。英文检索词为“mesenchymal stem cells,colorectal cancer,cancer stem cell,tumor microenvironment”,中文检索词为“间充质干细胞,结直肠癌,癌症干细胞,肿瘤微环境”,最终纳入119篇文献进行分析。结果与结论:(1)间充质干细胞对于结直肠癌具有促进和抑制的双面作用;(2)间充质干细胞的肿瘤归巢特性使其能够准确迁移到肿瘤位置并释放药物,基于这一特性,增加了治疗结直肠癌的安全性和有效性;(3)间充质干细胞衍生的外泌体作为良好的药物载体,在结直肠癌靶向治疗中显示出良好的应用前景;(4)使用病毒载体、非病毒载体或其他转染工具将具有成熟抗肿瘤作用的药物加载到间充质干细胞中,共同治疗结直肠癌;(5)间充质干细胞与化疗药物联合使用可以提高化疗药物疗效并降低化疗药物不良反应;(6)间充质干细胞促进结直肠癌的发展机制主要与结直肠癌细胞中的信号转导、趋化因子的表达状态及间充质干细胞向癌症相关成纤维细胞转化有关;(7)间充质干细胞可能具有驱动癌症干细胞的特性,促进肿瘤起始并提高肿瘤侵袭性;(8)间充质干细胞治疗结直肠癌还存在着不可避免的问题:缺乏标准化治疗方案及疗效评价方法、治疗成本高昂、间充质干细胞的保存与运输问题、间充质干细胞与化疗药物共同使用的比例等。

BACKGROUND:Early treatment methods for colorectal cancer include endoscopy and surgical resection,but there are many postoperative complications.Chemotherapy is the most common treatment for late-stage colorectal cancer,but chemotherapy can cause gastrointestinal dysfunction,bone marrow suppression,liver and kidney function damage,and other adverse reactions.As a result,most patients are not proactive and do not cooperate with treatment.OBJECTIVE:To review the mechanism of action,latest treatment progress,and current problems of mesenchymal stem cells in the treatment of colorectal cancer,and provide a basis for future clinical application.METHODS:PubMed,CNKI,and WanFang databases were searched for relevant literature using the keywords of“mesenchymal stem cells,colorectal cancer,cancer stem cell,tumor microenvironment”in Chinese and English,respectively.Finally,119 articles were included for analysis.RESULTS AND CONCLUSION:(1)Mesenchymal stem cells have both promoting and inhibiting effects on colorectal cancer.(2)The tumor homing characteristics of mesenchymal stem cells enable them to migrate accurately to the tumor site and release drugs,which increases the safety and effectiveness of the treatment of colorectal cancer.(3)Exosomes derived from mesenchymal stem cells can serve as good carriers and shows a good application prospect in the targeted therapy of colorectal cancer.(4)Using viral vectors,non-viral vectors,or other transfection tools,drugs with mature anti-tumor effects can be loaded into mesenchymal stem cells for the treatment of colorectal cancer.(5)The combined use of mesenchymal stem cells and chemotherapy drugs can improve the efficacy of chemotherapy drugs and reduce the adverse reactions of chemotherapy drugs.(6)The mechanism by which mesenchymal stem cells promote the development of colorectal cancer is mainly related to the expression status of signal transduction and chemotactic factors in colorectal cancer cells and the transformation of mesenchymal stem cells into cancer-related fibroblasts.(7)Mesenchymal stem cells may have the characteristics of driving cancer stem cells,promoting tumor initiation and increasing tumor invasion.(8)There are still some unavoidable problems in the treatment of colorectal cancer with mesenchymal stem cells:lack of standardized treatment plans and efficacy evaluation,high treatment costs,preservation and transportation of mesenchymal stem cells,and the proportion of combined use of mesenchymal stem cells and chemotherapy drugs.