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脂质体厚朴酚通过抑制自噬增强贝伐单抗对胶质母细胞瘤的抗肿瘤作用。

Liposomal honokiol enhance the anti-tumor effect of bevacizumab in glioblastoma by inhibiting autophagy.

作者信息

Xun Pei, Zong Jiabao, Li Shenglan, Li Wenbin

机构信息

Department of Neuro-Oncology , Cancer Center, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.

Department of Oncology, Beijing Daxing District People's Hospital, Beijing, China.

出版信息

Future Sci OA. 2025 Dec;11(1):2546232. doi: 10.1080/20565623.2025.2546232. Epub 2025 Aug 13.

DOI:10.1080/20565623.2025.2546232
PMID:40802280
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12351733/
Abstract

AIMS

To investigate whether liposomal honokiol enhances the anti-tumor effect of bevacizumab (BEV) in glioblastoma (GBM) and explore its underlying mechanism.

MATERIALS & METHODS: A U87 cell xenograft model in nude mice was used, with groups: model (M), M + liposomal honokiol (Lip-HNK), M + BEV, and M + Lip-HNK + BEV. Tumor volume, body weight, serum levels of VEGF, VEGFR, TNF-α, and Caspase-3, and expressions of autophagy-related (Beclin-1, LC3) and UPR-related (IRE1, GRP78) molecules in tumor tissues were detected.

RESULTS

Compared with monotherapy, the combination of Lip-HNK and BEV significantly reduced tumor volume and tumor index, decreased serum levels of VEGF, VEGFR, and TNF-α, while increasing serum caspase-3. Further mechanistic studies showed that the combination of Lip-HNK and BEV significantly reduced the expression of Beclin-1, LC3, IRE1, and GRP78 in tumors.

CONCLUSIONS

Lip-HNK may promote the anti-GBM effect of BEV by inhibiting autophagy mediated by the UPR response.

摘要

目的

研究脂质体厚朴酚是否能增强贝伐单抗(BEV)对胶质母细胞瘤(GBM)的抗肿瘤作用,并探讨其潜在机制。

材料与方法

采用U87细胞裸鼠异种移植模型,分为模型组(M)、M + 脂质体厚朴酚组(Lip-HNK)、M + BEV组和M + Lip-HNK + BEV组。检测肿瘤体积、体重、血清中VEGF、VEGFR、TNF-α和Caspase-3水平,以及肿瘤组织中自噬相关分子(Beclin-1、LC3)和未折叠蛋白反应(UPR)相关分子(IRE1、GRP78)的表达。

结果

与单一疗法相比,Lip-HNK与BEV联合使用显著降低了肿瘤体积和肿瘤指数,降低了血清中VEGF、VEGFR和TNF-α水平,同时提高了血清Caspase-3水平。进一步的机制研究表明,Lip-HNK与BEV联合使用显著降低了肿瘤中Beclin-1、LC3、IRE1和GRP78的表达。

结论

脂质体厚朴酚可能通过抑制UPR反应介导的自噬来促进BEV对GBM的抗肿瘤作用。

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