Qingjie Fuzheng Granule suppresses lymphangiogenesis in colorectal cancer via the VEGF-C/VEGFR-3 dependent PI3K/AKT pathway

Huang, Bin; Lu, Yao; Gui, Mengxuan; Guan, Jianhua; Mu, Lin; Zhao, Jinyan; Mao, Qianqian; Lin, Jiumao

doi:10.1016/j.biopha.2021.111331

Cited by 21 publications

(17 citation statements)

References 29 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Accumulating evidence suggests that the AKT-mediated signaling participates in lymphangiogeneis. It has been reported that Qingjie Fuzheng Granule inhibits lymphangiogenesis via the VEGF-C/VEGFR-3-dependent AKT pathway in colorectal cancer 30 . Treatment with human cathelicidin antimicrobial peptide LL-37 enhances lymphangiogenesis in lymphatic endothelial cells through the AKT and ERK signaling pathways 31 .…”

Section: Discussionmentioning

confidence: 99%

Extracellular Vesicles Derived From Hypoxia-Conditioned Adipose-Derived Mesenchymal Stem Cells Enhance Lymphangiogenesis

Yang

Liu

et al. 2022

Cell Transplant

View full text Add to dashboard Cite

Extracellular vesicles from adipose-derived mesenchymal stem cells (ADSCs) play an important role in lymphangiogenesis; however, the underlying mechanisms are not fully understood. In this study, we aimed to investigate the function of extracellular vesicles secreted by hypoxia-conditioned ADSCs in lymphangiogenesis and explore the potential molecular mechanisms. Extracellular vesicles were extracted from ADSCs cultured under hypoxia or normoxia conditions. The uptake of extracellular vesicles by lymphatic endothelial cells (LECs) was detected by immunofluorescence staining. The effects of extracellular vesicles on the viability, migration, and tube formation of LECs were determined by CCK-8 assay, migration assay, and tube formation assay, respectively. Molecules and pathway involved in lymphangiogenesis mediated by ADSC-derived extracellular vesicles were analyzed by luciferase reporter assay, qRT-polymerase chain reaction (PCR), and Western blot. Hypoxia ADSC-derived extracellular vesicles (H-ADSC/evs) significantly enhanced the proliferation, migration, and tube formation of LECs. Hypoxia decreased the expression of miR-129 in ADSC-derived extracellular vesicles. Overexpression of miR-129 counteracted the promoting effect of H-ADSC/evs on lymphangiogenesis. In addition, decreased exosomal miR-129 expression resulted in upregulation of HMGB1 in LECs, which led to AKT activation and lymphangiogenesis enhancement. Our data reveal that extracellular vesicles derived from hypoxia-conditioned ADSCs induce lymphangiogenesis, and this effect is mediated by miR-129/HMGB1/AKT signaling. Our findings imply that hypoxia ADSC-isolated extracellular vesicles may represent as a valuable target for the treatment of diseases associated with lymphatic remodeling.

show abstract

Section: Discussionmentioning

confidence: 99%

Extracellular Vesicles Derived From Hypoxia-Conditioned Adipose-Derived Mesenchymal Stem Cells Enhance Lymphangiogenesis

Yang

Liu

et al. 2022

Cell Transplant

View full text Add to dashboard Cite

show abstract

“…Cancer cells regulate HLECs by secreting cytokines such as VEGF-C, which is the key to tumor lymph node metastasis [7,10]. Tumor-related lymphangiogenesis is a promoter of tumor lymph node metastasis, which helps to promote the recruitment of cancer cells to lymph nodes [33].…”

Section: Discussionmentioning

confidence: 99%

“…Vascular endothelial growth factor C (VEGF-C) and vascular endothelial growth factor receptor 3 (VEGFR-3) play an important role in lymphangiogenesis [10,11]. Lymphatic vessel endothelial hyaluronan receptor-1 (LYVE-1) is one of the speci c markers of lymphatic endothelium.…”

Section: Introductionmentioning

confidence: 99%

ANRIL promotes the regulation of colorectal cancer on lymphatic endothelial cells via VEGF-C and is the key target for Pien Tze Huang to inhibit cancer metastasis

Lin

Huang²,

Lu³

et al. 2022

Preprint

Self Cite

View full text Add to dashboard Cite

lncRNA ANRIL is an oncogene, however the role of ANRIL in the regulation of colorectal cancer on human lymphatic endothelial cells (HLECs) is remain elusive. Pien Tze Huang (PZH, PTH) a Tradition Chinese Medicine (TCM) as an adjunctive medication could inhibit the cancer metastasis, however the mechanism still uncovering. We used network pharmacology, subcutaneous and orthotopic transplanted colorectal tumors models to determine the effect of PZH on tumor metastasis. Differential expressions of ANRIL in colorectal cancer cells, and stimulating the regulation of cancer cells on HLECs by culturing HLECs with cancer cells’ supernatants. Network pharmacology, transcriptomics, and rescue experiments were carried out to verify key targets of PZH. We found PZH interfered with 32.2% of disease genes and 76.7% of pathways, and inhibited the growth of colorectal tumors, liver metastasis, and the expression of ANRIL. The overexpression of ANRIL promoted the regulation of cancer cells on HLECs, leading to lymphangiogenesis, via upregulated VEGF-C secretion, and alleviated the effect of PZH on inhibiting the regulation of cancer cells on HLECs. Transcriptomic, network pharmacology and rescue experiments show that PI3K/AKT pathway is the most important pathway for PZH to affect tumor metastasis via ANRIL. In conclusion, PZH inhibits the regulation of colorectal cancer on HLECs to alleviate tumor lymphangiogenesis and metastasis by downregulating ANRIL dependent PI3K/AKT/VEGF-C pathway.

show abstract

“…Accumulating evidence suggests that the AKT-mediated signaling participates in lymphangiogeneis. It has been reported that Qingjie Fuzheng Granule inhibits lymphangiogenesis via the VEGF-C/VEGFR-3dependent AKT pathway in colorectal cancer [30]. Treatment with human cathelicidin antimicrobial peptide LL-37 enhances lymphangiogenesis in lymphatic endothelial cells through the AKT and ERK signaling pathways [31].…”

Section: Discussionmentioning

confidence: 99%

Exosomes Derived from Hypoxia-conditioned Adipose-derived Mesenchymal Stem Cells Enhance Lymphangiogenesis via Modulation of miR-129/HMGB1/AKT Pathway

Yang¹,

Li²,

Liu³

et al. 2021

Preprint

View full text Add to dashboard Cite

Background Exosomes from adipose-derived mesenchymal stem cells (ADSCs) play an important role in lymphangiogenesis; however, the underlying mechanisms are not fully understood. In this study, we aimed to investigate the function of exosomes secreted by hypoxia-conditioned ADSCs in lymphangiogenesis and explore the potential molecular mechanisms.Methods Exosomes were extracted from ADSCs cultured under hypoxia or normoxia conditions. The uptake of exosomes by LECs was detected by immunofluorescence staining. The effects of exosomes on the viability, migration, and tube formation of LECs were determined by CCK-8 assay, migration assay, and tube formation assay, respectively. Molecules and pathway involved in lymphangiogenesis mediated by ADSC-derived exosomes were analyzed by luciferase reporter assay, qRT-PCR, and Western blot.Results Hypoxia ADSC-derived exosomes (H-ADSC/exos) significantly enhanced the proliferation, migration, and tube formation of LECs. Hypoxia decreased the expression of miR-129 in ADSC-derived exosomes. Overexpression of miR-129 counteracted the promoting effect of H-ADSC/exos on lymphangiogenesis. In addition, decreased exosomal miR-129 expression resulted in upregulation of HMGB1 in LECs, which led to AKT activation and lymphangiogenesis enhancement. Our data reveal that exosomes derived from hypoxia-conditioned ADSCs induce lymphangiogenesis, and this effect is mediated by miR-129/HMGB1/AKT signaling. Conclusions Our findings imply that hypoxia ADSC-isolated exosomes may represent as a valuable target for the treatment of diseases associated with lymphatic remodeling.

show abstract

Qingjie Fuzheng Granule suppresses lymphangiogenesis in colorectal cancer via the VEGF-C/VEGFR-3 dependent PI3K/AKT pathway

Cited by 21 publications

References 29 publications

Extracellular Vesicles Derived From Hypoxia-Conditioned Adipose-Derived Mesenchymal Stem Cells Enhance Lymphangiogenesis

Extracellular Vesicles Derived From Hypoxia-Conditioned Adipose-Derived Mesenchymal Stem Cells Enhance Lymphangiogenesis

ANRIL promotes the regulation of colorectal cancer on lymphatic endothelial cells via VEGF-C and is the key target for Pien Tze Huang to inhibit cancer metastasis

Exosomes Derived from Hypoxia-conditioned Adipose-derived Mesenchymal Stem Cells Enhance Lymphangiogenesis via Modulation of miR-129/HMGB1/AKT Pathway

Contact Info

Product

Resources

About