收稿日期: 2024-12-31
网络出版日期: 2025-04-23
基金资助
广西自然科学基金资助项目(2024GXNSFAA010200);广西研究生教育创新计划项目(YCSW2023236)
Experimental study of doxorubicin coated by magnetic drug⁃carrying gel beads in the treatment of colorectal cancer
Received date: 2024-12-31
Online published: 2025-04-23
目的 探讨MgFe2O4和木薯淀粉为基材的铁基磁性淀粉载药凝胶珠在结直肠癌治疗中的作用。 方法 16只SPF级6周龄Balb/c雄性小鼠随机分为对照组、CMCS SA@MgFe2O4组、阿霉素组和CMCS SA@MgFe2O4@Dox组,每组4只,各组小鼠于种结直肠瘤(HCT116)后4、6、8、10、12、14 d分别给予生理盐水、CMCS SA@MgFe2O4、Doxorubicin 和CMCS SA@MgFe2O4@Dox口服。观察干预后不同时期各组肿瘤体积变化;采用TUNEL染色检测肿瘤组织凋亡情况;免疫组化检测肿瘤组织的Ki67、Caspase-3表达;Western blotting测定Caspase-3、Bcl-2、Bax蛋白表达。 结果 CMCS SA@MgFe2O4和对照组小鼠种植后的肿瘤体积随着饲养时间增长逐渐增大,而给予阿霉素组和CMCS SA@MgFe2O4@Dox组小鼠肿瘤体积和最终重量均降低(P < 0.05),组织间炎性细胞聚集,胶原纤维减少,细胞凋亡增加;Ki67表达减少(P < 0.05),Caspase-3表达增加(P < 0.05);Bcl-2蛋白表达下降(P < 0.05),Caspase-3和Bax蛋白表达上升(P < 0.05)。与Dox组相比,CMCS SA@MgFe2O4@Dox组小鼠肿瘤体积和最终质量更小(P < 0.05),组织坏死,胶原纤维减少,细胞凋亡进一步增加;Ki67表达更少(P < 0.05),Caspase-3表达更多(P < 0.05);Bcl-2蛋白表达进一步下降,Caspase-3和Bax蛋白表达进一步上升(P < 0.05)。 结论 铁基磁性淀粉载药系统对肿瘤细胞不具有治疗肿瘤作用,然而与阿霉素结合后,能明显增加阿霉素的治疗作用,减少其副作用。
孔蔺莎 , 何改改 , 李婷 , 方坤 , 何维 , 韦力 . 磁性载药凝胶珠包裹阿霉素治疗结直肠癌的实验研究[J]. 实用医学杂志, 2025 , 41(7) : 953 -959 . DOI: 10.3969/j.issn.1006-5725.2025.07.004
Objective To investigate the efficacy of ferro?based magnetic starch?loaded gel beads, composed of MgFe2O4 and cassava starch, in the treatment of colorectal cancer. Methods Sixteen SPF?grade 6?week?old male Balb/c mice were randomly assigned to four groups (n = 4 per group): control, CMCS SA@MgFe2O4, doxorubicin, and CMCS SA@MgFe2O4@Dox. Mice in each group received normal saline, CMCS SA@MgFe2O4, doxorubicin, or CMCS SA@MgFe2O4@Dox on days 4, 6, 8, 10, 12, and 14 post?implantation of colorectal tumor cells (HCT116). Tumor volume changes were monitored following treatment. TUNEL staining was performed to assess tumor tissue apoptosis. Immunohistochemistry was used to evaluate the expression levels of Ki67 and Caspase?3 in tumor tissues. Western blot was employed to determine the protein expression levels of Caspase?3, Bcl?2, and Bax. Results Mice in the Control and CMCS SA@MgFe2O4 groups exhibited the largest tumour volumes, with intact major organ structures, tightly arranged cells, normal nuclear morphology, and no significant inflammatory cell aggregation. In contrast, mice in the Dox group displayed shrunken tumour tissues, disorganized cardiac muscle fibres, enlarged interstitial spaces in splenic tissues, and inflammatory cell infiltration in liver, lung, and kidney tissues. Mice in the CMCS SA@MgFe2O4@Dox group showed minimal tumour tissue, well?aligned cardiac muscle fibres, and reduced inflammatory responses in the remaining organs. Compared to the Control group, mice in both the Dox and CMCS SA@MgFe2O4@Dox groups demonstrated significantly decreased tumour volume and final weight (P < 0.05), increased interstitial inflammatory cell aggregation, decreased collagen fibres, and enhanced apoptosis. Additionally, there was a significant decrease in Ki67 expression (P < 0.05) and an increase in Caspase?3 expression (P < 0.05). The expression of Bcl?2 protein was also significantly reduced (P < 0.05), while the expression of Caspase?3 and Bax proteins was significantly increased (P < 0.05). Compared to the Dox group, mice in the CMCS SA@MgFe2O4@Dox group exhibited significantly smaller tumour volume and final weight (P < 0.01), more pronounced tissue necrosis, further reduction in collagen fibres, and a greater increase in apoptosis. There was also a more significant decrease in Ki67 expression (P < 0.05) and a more substantial increase in Caspase?3 expression (P < 0.05). Furthermore, the expression of Bcl?2 protein was further decreased, while the expression of Caspase?3 and Bax proteins was further increased (P < 0.05). Conclusion The iron?based magnetic starch drug delivery system has no therapeutic effect on tumor cells, but the combination with adriamycin can significantly increase the therapeutic effect of adriamycin and reduce its side effects.
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