Research on predicting intestinal adverse reactions to chemotherapy drugs using mouse colon organoids
10.12354/j.issn.1000-8179.2024.20240278
- VernacularTitle:利用小鼠结肠类器官预测化疗药物肠道不良反应的研究
- Author:
Lei YING
1
;
Xu ENWEI
;
Bai ZHONGYUAN
;
Kang KEQING
;
Bai XUELIANG
;
Cui WEI
Author Information
1. 山西医科大学基础医学院(太原市 030001)
- Keywords:
organoid;
colorectal;
intestinal adverse reaction;
chemotherapy
- From:
Chinese Journal of Clinical Oncology
2024;51(9):447-453
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To predict the gastrointestinal side effects of chemotherapeutic drugs using healthy murine colon organoids.It aimed to identify safer alternative treatments for patients intolerant to certain chemotherapy regimens and demonstrate the potential clinical ap-plications of organoids in predicting gastrointestinal side effects.Methods:Healthy mouse colonic crypt cells were cultured in 3D.Paraffin sections of colon tissues and organoids were subsequently prepared,followed by haematoxylin and eosinand immunohistochemical staining(CDX2,Ki67,and CK19).The colonic organoids were treated with five chemotherapeutic drugs,and cell activity was assessed to determine their intestinal toxicity.The consistency of the incidence of gastrointestinal side effects observed in this study and in clinical practice were analyzed by comparing the results to the published literature.Results:The histological characteristics of the colon organoids were highly consistent with those of the original colon tissues.The tolerance of normal colon organoids to different chemotherapeutic drugs was vari-able.Capecitabine had the least cytotoxic effect on mouse colon organoids,whereas paclitaxel liposomes showed the strongest cytotoxic ef-fect when IC50 was the only consideration.Considering clinical drug concentrations,a significant difference was observed in the organoid in-hibition rates between albumin paclitaxel and liposomal paclitaxel.Statistical analysis of clinical trial data showed that the incidence of gradeⅢ/Ⅳ diarrhea caused by albumin paclitaxel,epirubicin,capecitabine,and cyclophosphamide was consistent with the corresponding or-ganoid inhibition rates.Conclusions:Combining clinical drug doses,we recommend prioritizing albumin paclitaxel and avoiding the use of liposomal paclitaxel to improve chemotherapy tolerance.This study demonstrates that normal colon organoids can effectively predict the occurrence of severe diarrhea associated with most chemotherapeutic drugs.
