Homogeneous polyporus polysaccharide inhibits bladder cancer by polarizing macrophages to M1 subtype in tumor microenvironment

Abstract Background Polyporus polysaccharide (PPS), an active ingredient of traditional Chinese medicinal Polyporus umbellatus, has multiple biological functions, such as anti-cancer, immune-regulating and hepatoprotective activities. The purpose of this study was to investigate the mechanism of hom...

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Main Authors: Wenyu Jia, Siwan Luo, Gena Lai, Shiqi Li, Shuai Huo, Meifang Li, Xing Zeng
Format: Article
Language:English
Published: BMC 2021-05-01
Series:BMC Complementary Medicine and Therapies
Subjects:
Online Access:https://doi.org/10.1186/s12906-021-03318-x
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author Wenyu Jia
Siwan Luo
Gena Lai
Shiqi Li
Shuai Huo
Meifang Li
Xing Zeng
author_facet Wenyu Jia
Siwan Luo
Gena Lai
Shiqi Li
Shuai Huo
Meifang Li
Xing Zeng
author_sort Wenyu Jia
collection DOAJ
description Abstract Background Polyporus polysaccharide (PPS), an active ingredient of traditional Chinese medicinal Polyporus umbellatus, has multiple biological functions, such as anti-cancer, immune-regulating and hepatoprotective activities. The purpose of this study was to investigate the mechanism of homogeneous polyporus polysaccharide (HPP) activated macrophages in the treatment of bladder cancer. Methods 100 ng/mL Phorbol myristate acetate (PMA) was used to induce THP-1 human leukemic cells as a macrophage model. Then macrophages derived from THP-1 were treated with different concentrations of HPP (1, 10 and 100 μg/mL). Flow cytometry and RT-PCR were used to detected the expression of CD16, CD23, CD86, CD40 and interleukin (IL)-Iβ, iNOS mRNA. ELISA was used to test the change of IL-1β and TNF-α in macrophage after the treatment with HPP. The conditioned medium from HPP-polarized macrophages was used to detect the effect of activated macrophages on bladder cancer. MTT assay, 5-ethynyl-2′-deoxyuridine assay, flow cytometry, Transwell assay, and Western blot analysis were used to detect the effects of polarized macrophages on the viability, proliferation, apoptosis, and migration of bladder cancer cells. Western blot was also used to analysis the change of JAK2/NF-κB pathway protein. Results HPP promoted the expression of pro-inflammatory factors, such as IL-Iβ, TNF-α and iNOS, and surface molecules CD86, CD16, CD23, and CD40 in macrophages and then polarized macrophages to M1 type. Results demonstrated that activated macrophages inhibited the proliferation of bladder cancer cells, regulated their apoptosis, and inhibited migration and epithelial–mesenchymal transformation (EMT). JAK2/NF-κB pathways were downregulated in the anti-bladder cancer process of activated macrophages. Conclusion The findings indicated that HPP inhibited the proliferation and progression of bladder cancer by the polarization of macrophages to M1 type, and JAK2/NF-κB pathway was downregulated in the process of anti-bladder cancer.
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spelling doaj.art-8ccadf28920b4655b0473387d6d0ac0e2022-12-21T22:11:56ZengBMCBMC Complementary Medicine and Therapies2662-76712021-05-0121111210.1186/s12906-021-03318-xHomogeneous polyporus polysaccharide inhibits bladder cancer by polarizing macrophages to M1 subtype in tumor microenvironmentWenyu Jia0Siwan Luo1Gena Lai2Shiqi Li3Shuai Huo4Meifang Li5Xing Zeng6The Second Affiliated Hospital, Guangzhou University of Chinese MedicineThe Second Affiliated Hospital, Guangzhou University of Chinese MedicineThe Second Affiliated Hospital, Guangzhou University of Chinese MedicineThe Second Affiliated Hospital, Guangzhou University of Chinese MedicineThe Second Affiliated Hospital, Guangzhou University of Chinese MedicineThe Second Affiliated Hospital, Guangzhou University of Chinese MedicineThe Second Affiliated Hospital, Guangzhou University of Chinese MedicineAbstract Background Polyporus polysaccharide (PPS), an active ingredient of traditional Chinese medicinal Polyporus umbellatus, has multiple biological functions, such as anti-cancer, immune-regulating and hepatoprotective activities. The purpose of this study was to investigate the mechanism of homogeneous polyporus polysaccharide (HPP) activated macrophages in the treatment of bladder cancer. Methods 100 ng/mL Phorbol myristate acetate (PMA) was used to induce THP-1 human leukemic cells as a macrophage model. Then macrophages derived from THP-1 were treated with different concentrations of HPP (1, 10 and 100 μg/mL). Flow cytometry and RT-PCR were used to detected the expression of CD16, CD23, CD86, CD40 and interleukin (IL)-Iβ, iNOS mRNA. ELISA was used to test the change of IL-1β and TNF-α in macrophage after the treatment with HPP. The conditioned medium from HPP-polarized macrophages was used to detect the effect of activated macrophages on bladder cancer. MTT assay, 5-ethynyl-2′-deoxyuridine assay, flow cytometry, Transwell assay, and Western blot analysis were used to detect the effects of polarized macrophages on the viability, proliferation, apoptosis, and migration of bladder cancer cells. Western blot was also used to analysis the change of JAK2/NF-κB pathway protein. Results HPP promoted the expression of pro-inflammatory factors, such as IL-Iβ, TNF-α and iNOS, and surface molecules CD86, CD16, CD23, and CD40 in macrophages and then polarized macrophages to M1 type. Results demonstrated that activated macrophages inhibited the proliferation of bladder cancer cells, regulated their apoptosis, and inhibited migration and epithelial–mesenchymal transformation (EMT). JAK2/NF-κB pathways were downregulated in the anti-bladder cancer process of activated macrophages. Conclusion The findings indicated that HPP inhibited the proliferation and progression of bladder cancer by the polarization of macrophages to M1 type, and JAK2/NF-κB pathway was downregulated in the process of anti-bladder cancer.https://doi.org/10.1186/s12906-021-03318-xBladder cancerHomogeneous polyporus polysaccharideTHP-1-derived macrophageTumor microenvironmentJAK2/NF-κB pathway
spellingShingle Wenyu Jia
Siwan Luo
Gena Lai
Shiqi Li
Shuai Huo
Meifang Li
Xing Zeng
Homogeneous polyporus polysaccharide inhibits bladder cancer by polarizing macrophages to M1 subtype in tumor microenvironment
BMC Complementary Medicine and Therapies
Bladder cancer
Homogeneous polyporus polysaccharide
THP-1-derived macrophage
Tumor microenvironment
JAK2/NF-κB pathway
title Homogeneous polyporus polysaccharide inhibits bladder cancer by polarizing macrophages to M1 subtype in tumor microenvironment
title_full Homogeneous polyporus polysaccharide inhibits bladder cancer by polarizing macrophages to M1 subtype in tumor microenvironment
title_fullStr Homogeneous polyporus polysaccharide inhibits bladder cancer by polarizing macrophages to M1 subtype in tumor microenvironment
title_full_unstemmed Homogeneous polyporus polysaccharide inhibits bladder cancer by polarizing macrophages to M1 subtype in tumor microenvironment
title_short Homogeneous polyporus polysaccharide inhibits bladder cancer by polarizing macrophages to M1 subtype in tumor microenvironment
title_sort homogeneous polyporus polysaccharide inhibits bladder cancer by polarizing macrophages to m1 subtype in tumor microenvironment
topic Bladder cancer
Homogeneous polyporus polysaccharide
THP-1-derived macrophage
Tumor microenvironment
JAK2/NF-κB pathway
url https://doi.org/10.1186/s12906-021-03318-x
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