Calf Thymus Polypeptide Restrains the Growth of Colorectal Tumor via Regulating the Intestinal Microbiota-Mediated Immune Function
Calf thymus polypeptide (CTP), with a molecular mass of <10 kDa, is prepared from the thymus of less than 30-day-old newborn cattle. In the present study, the inhibitory function of CTP in colorectal cancer (CRC) was investigated in B6/JGpt-Apcem1Cin(MinC)/Gpt (ApcMin/+) mice. CTP hampered tu...
Main Authors: | , , , , , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
Frontiers Media S.A.
2022-05-01
|
Series: | Frontiers in Pharmacology |
Subjects: | |
Online Access: | https://www.frontiersin.org/articles/10.3389/fphar.2022.898906/full |
_version_ | 1811257844304969728 |
---|---|
author | Lanzhou Li Lanzhou Li Chenfei Zhao Fange Kong Yi-Cong Li Chunxia Wang Shanshan Chen Hor-Yue Tan Yang Liu Di Wang Di Wang |
author_facet | Lanzhou Li Lanzhou Li Chenfei Zhao Fange Kong Yi-Cong Li Chunxia Wang Shanshan Chen Hor-Yue Tan Yang Liu Di Wang Di Wang |
author_sort | Lanzhou Li |
collection | DOAJ |
description | Calf thymus polypeptide (CTP), with a molecular mass of <10 kDa, is prepared from the thymus of less than 30-day-old newborn cattle. In the present study, the inhibitory function of CTP in colorectal cancer (CRC) was investigated in B6/JGpt-Apcem1Cin(MinC)/Gpt (ApcMin/+) mice. CTP hampered tumor development and enhanced the ratio of CD3e−NK1.1+ cells by 113.0% and CD3e+CD28+ cells by 84.7% in the peripheral blood of ApcMin/+ mice. CTP improved the richness, diversity, and evenness of the intestinal microbiota of ApcMin/+ mice, particularly by regulating the abundance of immune-related microorganisms. CTP effectively regulated the expression of immune-related cytokines, such as interleukin (IL)-2 (15.19% increment), IL-12 (17.47% increment), and transforming growth factor (TGF)-β (11.19% reduction). Additionally, it enhanced the levels of CD4 and CD8, as well as the ratio of helper T lymphocytes (Th)1/Th2 in the spleen and tumors of ApcMin/+ mice. In CTP-treated mice, reduced levels of programmed death-1 (PD-1), programmed cell death-ligand 1 (PD-L1), cytotoxic T lymphocyte-associated antigen 4 (CTLA4), activated nuclear factor of activated T cells 1 (NFAT1), and nuclear factor κB (NF-κB) p65 signaling were noted. Collectively, the anti-CRC effect of CTP is related to the modulation of intestinal microbiota-mediated immune function, which provides a reference for CTP as a therapeutic drug or a combination drug used in CRC treatment in a clinical setting. |
first_indexed | 2024-04-12T18:03:53Z |
format | Article |
id | doaj.art-0060434f707f48278ccc6a8124dad54d |
institution | Directory Open Access Journal |
issn | 1663-9812 |
language | English |
last_indexed | 2024-04-12T18:03:53Z |
publishDate | 2022-05-01 |
publisher | Frontiers Media S.A. |
record_format | Article |
series | Frontiers in Pharmacology |
spelling | doaj.art-0060434f707f48278ccc6a8124dad54d2022-12-22T03:22:03ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122022-05-011310.3389/fphar.2022.898906898906Calf Thymus Polypeptide Restrains the Growth of Colorectal Tumor via Regulating the Intestinal Microbiota-Mediated Immune FunctionLanzhou Li0Lanzhou Li1Chenfei Zhao2Fange Kong3Yi-Cong Li4Chunxia Wang5Shanshan Chen6Hor-Yue Tan7Yang Liu8Di Wang9Di Wang10Engineering Research Center of Chinese Ministry of Education for Edible and Medicinal Fungi, Jilin Agricultural University, Changchun, ChinaSchool of Life Sciences, Jilin University, Changchun, ChinaEngineering Research Center of Chinese Ministry of Education for Edible and Medicinal Fungi, Jilin Agricultural University, Changchun, ChinaEngineering Research Center of Chinese Ministry of Education for Edible and Medicinal Fungi, Jilin Agricultural University, Changchun, ChinaEngineering Research Center of Chinese Ministry of Education for Edible and Medicinal Fungi, Jilin Agricultural University, Changchun, ChinaEngineering Research Center of Chinese Ministry of Education for Edible and Medicinal Fungi, Jilin Agricultural University, Changchun, ChinaSchool of Life Sciences, Jilin University, Changchun, ChinaCentre for Chinese Herbal Medicine Drug Development, School of Chinese Medicine, Hong Kong Baptist University, Hong Kong, ChinaEngineering Research Center of Chinese Ministry of Education for Edible and Medicinal Fungi, Jilin Agricultural University, Changchun, ChinaEngineering Research Center of Chinese Ministry of Education for Edible and Medicinal Fungi, Jilin Agricultural University, Changchun, ChinaSchool of Life Sciences, Jilin University, Changchun, ChinaCalf thymus polypeptide (CTP), with a molecular mass of <10 kDa, is prepared from the thymus of less than 30-day-old newborn cattle. In the present study, the inhibitory function of CTP in colorectal cancer (CRC) was investigated in B6/JGpt-Apcem1Cin(MinC)/Gpt (ApcMin/+) mice. CTP hampered tumor development and enhanced the ratio of CD3e−NK1.1+ cells by 113.0% and CD3e+CD28+ cells by 84.7% in the peripheral blood of ApcMin/+ mice. CTP improved the richness, diversity, and evenness of the intestinal microbiota of ApcMin/+ mice, particularly by regulating the abundance of immune-related microorganisms. CTP effectively regulated the expression of immune-related cytokines, such as interleukin (IL)-2 (15.19% increment), IL-12 (17.47% increment), and transforming growth factor (TGF)-β (11.19% reduction). Additionally, it enhanced the levels of CD4 and CD8, as well as the ratio of helper T lymphocytes (Th)1/Th2 in the spleen and tumors of ApcMin/+ mice. In CTP-treated mice, reduced levels of programmed death-1 (PD-1), programmed cell death-ligand 1 (PD-L1), cytotoxic T lymphocyte-associated antigen 4 (CTLA4), activated nuclear factor of activated T cells 1 (NFAT1), and nuclear factor κB (NF-κB) p65 signaling were noted. Collectively, the anti-CRC effect of CTP is related to the modulation of intestinal microbiota-mediated immune function, which provides a reference for CTP as a therapeutic drug or a combination drug used in CRC treatment in a clinical setting.https://www.frontiersin.org/articles/10.3389/fphar.2022.898906/fullcalf thymus polypeptidecolorectal cancerintestinal microbiotaT cellsNK cellsinterleukin-2 |
spellingShingle | Lanzhou Li Lanzhou Li Chenfei Zhao Fange Kong Yi-Cong Li Chunxia Wang Shanshan Chen Hor-Yue Tan Yang Liu Di Wang Di Wang Calf Thymus Polypeptide Restrains the Growth of Colorectal Tumor via Regulating the Intestinal Microbiota-Mediated Immune Function Frontiers in Pharmacology calf thymus polypeptide colorectal cancer intestinal microbiota T cells NK cells interleukin-2 |
title | Calf Thymus Polypeptide Restrains the Growth of Colorectal Tumor via Regulating the Intestinal Microbiota-Mediated Immune Function |
title_full | Calf Thymus Polypeptide Restrains the Growth of Colorectal Tumor via Regulating the Intestinal Microbiota-Mediated Immune Function |
title_fullStr | Calf Thymus Polypeptide Restrains the Growth of Colorectal Tumor via Regulating the Intestinal Microbiota-Mediated Immune Function |
title_full_unstemmed | Calf Thymus Polypeptide Restrains the Growth of Colorectal Tumor via Regulating the Intestinal Microbiota-Mediated Immune Function |
title_short | Calf Thymus Polypeptide Restrains the Growth of Colorectal Tumor via Regulating the Intestinal Microbiota-Mediated Immune Function |
title_sort | calf thymus polypeptide restrains the growth of colorectal tumor via regulating the intestinal microbiota mediated immune function |
topic | calf thymus polypeptide colorectal cancer intestinal microbiota T cells NK cells interleukin-2 |
url | https://www.frontiersin.org/articles/10.3389/fphar.2022.898906/full |
work_keys_str_mv | AT lanzhouli calfthymuspolypeptiderestrainsthegrowthofcolorectaltumorviaregulatingtheintestinalmicrobiotamediatedimmunefunction AT lanzhouli calfthymuspolypeptiderestrainsthegrowthofcolorectaltumorviaregulatingtheintestinalmicrobiotamediatedimmunefunction AT chenfeizhao calfthymuspolypeptiderestrainsthegrowthofcolorectaltumorviaregulatingtheintestinalmicrobiotamediatedimmunefunction AT fangekong calfthymuspolypeptiderestrainsthegrowthofcolorectaltumorviaregulatingtheintestinalmicrobiotamediatedimmunefunction AT yicongli calfthymuspolypeptiderestrainsthegrowthofcolorectaltumorviaregulatingtheintestinalmicrobiotamediatedimmunefunction AT chunxiawang calfthymuspolypeptiderestrainsthegrowthofcolorectaltumorviaregulatingtheintestinalmicrobiotamediatedimmunefunction AT shanshanchen calfthymuspolypeptiderestrainsthegrowthofcolorectaltumorviaregulatingtheintestinalmicrobiotamediatedimmunefunction AT horyuetan calfthymuspolypeptiderestrainsthegrowthofcolorectaltumorviaregulatingtheintestinalmicrobiotamediatedimmunefunction AT yangliu calfthymuspolypeptiderestrainsthegrowthofcolorectaltumorviaregulatingtheintestinalmicrobiotamediatedimmunefunction AT diwang calfthymuspolypeptiderestrainsthegrowthofcolorectaltumorviaregulatingtheintestinalmicrobiotamediatedimmunefunction AT diwang calfthymuspolypeptiderestrainsthegrowthofcolorectaltumorviaregulatingtheintestinalmicrobiotamediatedimmunefunction |