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多糖与PD1抗体联合治疗增强结直肠癌异种移植小鼠的抗肿瘤疗效。

Polysaccharide and PD1-Antibody Combination Therapy Enhances Antitumor Efficacy in Colorectal Cancer-Xenograft Mice.

作者信息

Li Jinxia, Wang Yiping, Jin Weiyang, Shen Li

机构信息

College of Traditional Chinese Medicine, Hunan University of Chinese Medicine, Changsha, 410208, People's Republic of China.

Key Laboratory of Digestive Pathophysiology of Zhejiang Province, First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, 310006, People's Republic of China.

出版信息

Onco Targets Ther. 2021 Feb 24;14:1239-1248. doi: 10.2147/OTT.S294253. eCollection 2021.

DOI:10.2147/OTT.S294253
PMID:33658792
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7917333/
Abstract

OBJECTIVE

To observe the efficacy of polysaccharide (AEPS) combined with PD1 antibody therapy in colorectal cancer-xenograft mice.

METHODS

CT26 cells were inoculated into 80 C57BL/6 mice to establish the colorectal cancer xenograft-mouse model. Mice were divided evenly into a model group, AEPS group, anti-PD1 group, and combined group. AEPS 5mL/kg•day was given orally and 10 mg/kg anti-PD1 injected intravenously for 28 days. Tumor growth and mouse survival were observed. Tumor-cell proliferation and metastasis markers Ki67, N-cadherin, KLF4, and Oct4 were detected with immunochemistry and Western blotting, T-cell infiltration in spleens and tumors was detected with MTT and flow cytometry. IFNγ and TNFα were detected with ELISA.

RESULTS

Tumor growth was significantly retarded and survival prolonged in the AEPS, anti-PD1, and combined groups. Ki67 expression decreased in the anti-PD1 and combined groups, and N-cadherin, KLF4, and Oct4 expression decreased in the AEPS and combined groups. IFNγ and TNFα levels, T-cell infiltration in spleen, and tumor all increased distinctively in the AEPS and combined groups. The combined group showed better antitumor effects and life-extension effect than the other two groups.

CONCLUSION

AEPS and PD1 antibody-combination therapy can suppresses tumor growth and prolong survival of colorectal cancer-xenograft mice by regulating immunofunction, and the combined therapy showed better therapeutic efficacy than the single treatment.

摘要

目的

观察多糖(AEPS)联合PD1抗体治疗对结直肠癌异种移植小鼠的疗效。

方法

将CT26细胞接种到80只C57BL/6小鼠体内,建立结直肠癌异种移植小鼠模型。将小鼠平均分为模型组、AEPS组、抗PD1组和联合组。口服给予AEPS 5mL/kg•天,静脉注射10mg/kg抗PD1,持续28天。观察肿瘤生长和小鼠存活情况。用免疫化学和蛋白质印迹法检测肿瘤细胞增殖和转移标志物Ki67、N-钙黏蛋白、KLF4和Oct4,用MTT法和流式细胞术检测脾脏和肿瘤中的T细胞浸润情况。用ELISA法检测IFNγ和TNFα。

结果

AEPS组、抗PD1组和联合组的肿瘤生长明显受到抑制,存活时间延长。抗PD1组和联合组中Ki67表达降低,AEPS组和联合组中N-钙黏蛋白、KLF4和Oct4表达降低。AEPS组和联合组中IFNγ和TNFα水平、脾脏T细胞浸润和肿瘤均明显增加。联合组的抗肿瘤效果和延长生命效果优于其他两组。

结论

AEPS与PD1抗体联合治疗可通过调节免疫功能抑制结直肠癌异种移植小鼠的肿瘤生长并延长其存活时间,联合治疗的疗效优于单一治疗。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4001/7917333/6767c260f004/OTT-14-1239-g0006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4001/7917333/79ac44e41ea9/OTT-14-1239-g0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4001/7917333/d7c1f26731ae/OTT-14-1239-g0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4001/7917333/0a050cb30686/OTT-14-1239-g0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4001/7917333/be51a8f211da/OTT-14-1239-g0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4001/7917333/d38633d93363/OTT-14-1239-g0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4001/7917333/6767c260f004/OTT-14-1239-g0006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4001/7917333/79ac44e41ea9/OTT-14-1239-g0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4001/7917333/d7c1f26731ae/OTT-14-1239-g0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4001/7917333/0a050cb30686/OTT-14-1239-g0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4001/7917333/be51a8f211da/OTT-14-1239-g0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4001/7917333/d38633d93363/OTT-14-1239-g0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4001/7917333/6767c260f004/OTT-14-1239-g0006.jpg

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