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通过热敏凝胶负载去氢骆驼蓬碱改善结直肠癌治疗的抗肿瘤效果

Improving anti-tumor outcomes for colorectal cancer therapy through thermosensitive gel loading harmine.

作者信息

Li Zhenzhen, Chen Liqing, He Chenghui, Han Ying, Han Mingfeng, Zhang Yingying, Qi Lingling, Xing Xuezhong, Huang Wei, Gao Zhonggao, Xing Jianguo

机构信息

Key Laboratory of Xinjiang Endemic Phytomedicine Resources of Ministry of Education, School of Pharmacy, Shihezi University Shihezi 832003, China.

State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Department of Pharmaceutics, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College Beijing 100050, China.

出版信息

Am J Transl Res. 2020 May 15;12(5):1658-1671. eCollection 2020.

Abstract

Colorectal cancer is a common malignant tumor that seriously endangers human health. Harmine (HM), a natural product, has been shown to have a significant inhibitory effect on various cancers. However, systemic injection of HM can cause central nervous toxicity, which limits its clinical application. Local administration of HM overcomes this problem to a certain extent. In this study, we prepared an thermosensitive HM gel preparation (HM gel), and used it to treat colon cancer with reduced toxic side effects and prolonged residence time of HM at the tumor site. We employed a central composite design and response surface methodology to optimize the formulation, and evaluated the physicochemical properties, rectal retention capacity, and and antitumor effects of HM gel on colon 26 tumor cells. The results showed that HM gel had a significant inhibitory effect on the growth of colon 26 cells . In an orthotopic tumor-bearing mouse model, HM gel exhibited an obvious inhibitory effect on tumor growth and metastasis, and significantly prolonged the survival period. In conclusion, HM gel exhibited significant anti-tumor effects on colon cancer, and therefore presents a promising formulation for the treatment of colorectal cancer.

摘要

结直肠癌是一种严重危害人类健康的常见恶性肿瘤。哈尔明碱(HM)是一种天然产物,已被证明对多种癌症具有显著的抑制作用。然而,全身注射HM会引起中枢神经毒性,这限制了其临床应用。局部给药HM在一定程度上克服了这个问题。在本研究中,我们制备了一种热敏性HM凝胶制剂(HM凝胶),并用其治疗结肠癌,降低了毒副作用,延长了HM在肿瘤部位的滞留时间。我们采用中心复合设计和响应面法优化配方,并评估了HM凝胶的理化性质、直肠滞留能力以及对结肠26肿瘤细胞的抗肿瘤作用。结果表明,HM凝胶对结肠26细胞的生长具有显著的抑制作用。在原位荷瘤小鼠模型中,HM凝胶对肿瘤生长和转移表现出明显的抑制作用,并显著延长了生存期。总之,HM凝胶对结肠癌表现出显著的抗肿瘤作用,因此是一种有前途的结直肠癌治疗制剂。

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