南方医科大学学报

南方医科大学学报 ›› 2023, Vol. 43 ›› Issue (6): 873-878.doi: 10.12122/j.issn.1673-4254.2023.06.01

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蛹虫草代谢产物虫草素抑制舌鳞癌裸鼠移植瘤的生长

郑庆委，邵一丹，郑婉婷，邹映雪   

  1. 感染与免疫安徽普通高校重点实验室（蚌埠医学院），安徽 蚌埠 233030；天津大学医学工程与转化医学研究院，天津 300072；天津市儿童医院，天津 30074
  • 出版日期:2023-06-20 发布日期:2023-07-07

Cordycepin, a metabolite of Cordyceps militaris, inhibits xenograft tumor growth of tongue squamous cell carcinoma in nude mice

ZHENG Qingwei, SHAO Yidan, ZHENG Wanting, ZOU Yingxue   

  1. Key Laboratory of Infection and Immunity of Anhui Higher Education Institutes, Bengbu Medical College, Bengbu 233030, China; Academy of Medical Engineering and Translational Medicine, Tianjin University, Tianjin 300072, China; Children's Hospital of Tianjin University, Tianjin 30074, China
  • Online:2023-06-20 Published:2023-07-07

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摘要： 目的 评估虫草素对口腔癌的抑制作用并探讨其作用机制。方法 将人口腔癌TCA-8113细胞接种于BALB/c裸鼠皮下，建立口腔癌裸鼠模型。将裸鼠模型其随机分为模型组和虫草素组，进行为期4周的治疗，之后切除肿瘤并称重，评估虫草素的抗肿瘤效果。通过HE染色评估小鼠心脏、脾脏、肝脏、肾脏和肺部的组织学变化，TUNEL染色检测肿瘤细胞死亡，并通过RT-qPCR和Western blotting评估Bax、Bcl-2、GRP78、CHOP和caspase-12的表达。结果 虫草素治疗可使裸鼠皮下肿瘤生长减少56.09%。此外，虫草素治疗还与肿瘤细胞形态和凋亡死亡的显著变化相关，治疗后荷瘤裸鼠主要器官的形态未发生任何变化。虫草素处理还显著降低了Bcl-2的表达（P<0.05），同时增加了Bax、GRP78、CHOP和caspase-12 RNA和蛋白质水平的表达。结论 虫草素可通过内源性线粒体途径和内质网应激途径诱导TCA-8113细胞凋亡。

关键词: 虫草素；食用菌；蛹虫草；口腔癌；细胞凋亡；异种移植物

Abstract: Objective To evaluate the inhibitory effect of cordycepin on oral cancer xenograft in nude mice and explore the underlying mechanisms. Methods Sixteen BALB/c mice bearing subcutaneous human tongue squamous cell carcinoma (TSCC) TCA-8113 cell xenografts were randomized into model group and cordycepin treatment group for daily treatment with saline and cordycepin for 4 weeks. After the treatment, the tumor xenografts were dissected and weighed to assess the tumor inhibition rate. Histological changes in the heart, spleen, liver, kidney, and lung of the mice were evaluated with HE staining, and tumor cell apoptosis was examined using TUNEL staining; The expressions of Bax, Bcl-2, GRP78, CHOP, and caspase-12 in the xenografts were detected using RT-qPCR and Western blotting. Results Cordycepin treatmentresulted in a tumor inhibition rate of 56.09% in the nude mouse models, induced obvious changes in tumor cell morphology and significantly enhanced apoptotic death of the tumor cells without causing pathological changes in the vital organs. Cordycepin treatment also significantly reduced Bcl-2 expression (P<0.05) and increased Bax, GRP78, CHOP, and caspase-12 expressions at both the RNA and protein levels in the tumor tissues. Conclusion Cordycepin treatment can induce apoptotic death of TCA-8113 cell xenografts in nude mice via the endogenous mitochondrial pathway and endoplasmic reticulum stress pathways.

Key words: cordycepin; edible fungi; Cordyceps militaris; oral cancer; cell apoptosis; xenograft