This is a preprint, a preliminary version of a manuscript that has not completed peer review at a journal. Research Square does not conduct peer review prior to posting preprints. The posting of a preprint on this server should not be interpreted as an endorsement of its validity or suitability for dissemination as established information or for guiding clinical practice.
Research
Fu-Zheng-Jie-Du Ointment Enhances the Therapeutic Efficacy of 5-fluoropyrimidine by Inhibiting TIE2-expressing Monocyte/macrophage-mediated Angiogenesis in a Mouse Gastric Cancer Model
Jie Lj
Department of Oncology, Guang’anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, 10053, China
Corresponding Author
ORCiD: https://orcid.org/0000-0002-3461-8816
License:
This work is licensed under a CC BY 4.0 License. Read Full License
Background: Most cases of gastric cancer (GC), which is one of the most common cancers in China, are diagnosed at an advanced stage. The first-line treatments for GC include 5-fluoropyrimidine (5-FU)-based chemotherapy. However, the cancer cells may develop 5-FU resistance. The inhibition of angiogenesis can be an alternative therapeutic strategy for GC. Recent studies have demonstrated that TIE2-expressing monocytes/macrophages (TEMs), a subtype of tumor-associated macrophages (TAMs), exhibit profound pro-angiogenic activity. The herbs used in traditional Chinese medicine can be a potential source of anti-cancer agents and can improve the therapeutic efficacy of chemotherapy drugs. In this study, the role of TEMs in the synergistic anti-cancer effects of Fu-Zheng-Jie-Du ointment (FZJD) and 5-FU was evaluated.
Methods: The migration of TEMs was evaluated using the transwell assay. Tube formation assay and quantitative real-time polymerase chain reaction analysis were used to determine the pro-angiogenic activity of TEMs. Tumor-bearing mouse model and immunohistofluorescence stain were used to evaluate the anti-tumor effect of FZJD and the underlying mechanism.
Results: FZJD inhibited the migration and pro-angiogenic activity of TEMs. Additionally, tumor growth in the mice co-treated with FZJD and 5-FU was lower than that in the mice treated with FZJD or 5-FU. Immunohistofluorescence stain revealed that the migration of TEMs was not inhibited upon treatment with FZJD alone or in combination with 5-FU. Moreover, treatment with FZJD did not decrease the endothelial cell population. In contrast, the treatment combination of FZJD and 5-FU markedly decreased the endothelial cell population.
Conclusions: FZJD improves the anti-cancer efficacy of 5-FU through the inhibition of TEM-mediated angiogenesis.
Keywords
gastric cancer, Fu-Zheng-Jie-Du ointment, TIE2-expressing monocytes/macrophages, angiogenesis, chemotherapy
Figure 1
Figure 2
Figure 3
Figure 4
Badges
Prescreen
This manuscript passed our Prescreen assessment
Complete author information
Appropriate declaration statements
Potential risks to human health
Prescreen
History
CURRENT STATUS: Posted
Version 1
Posted 17 Sep, 2020
No community comments so far
Metrics
Comments: 0
PDF Downloads: ...
HTML Views: ...
Subject Areas
Internal Medicine
Learn more about our company.
This is a preprint. It has not completed peer review.
Research
Fu-Zheng-Jie-Du Ointment Enhances the Therapeutic Efficacy of 5-fluoropyrimidine by Inhibiting TIE2-expressing Monocyte/macrophage-mediated Angiogenesis in a Mouse Gastric Cancer Model
Jie Lj
Department of Oncology, Guang’anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, 10053, China
Corresponding Author
ORCiD: https://orcid.org/0000-0002-3461-8816
Badges
Prescreen
This manuscript passed our Prescreen assessment
Complete author information
Appropriate declaration statements
Potential risks to human health
Prescreen
History
CURRENT STATUS: Posted
Version 1
Posted 17 Sep, 2020
No community comments so far
Metrics
Comments: 0
PDF Downloads: ...
HTML Views: ...
Subject Areas
Internal Medicine
License:
This work is licensed under a CC BY 4.0 License. Read Full License
Background: Most cases of gastric cancer (GC), which is one of the most common cancers in China, are diagnosed at an advanced stage. The first-line treatments for GC include 5-fluoropyrimidine (5-FU)-based chemotherapy. However, the cancer cells may develop 5-FU resistance. The inhibition of angiogenesis can be an alternative therapeutic strategy for GC. Recent studies have demonstrated that TIE2-expressing monocytes/macrophages (TEMs), a subtype of tumor-associated macrophages (TAMs), exhibit profound pro-angiogenic activity. The herbs used in traditional Chinese medicine can be a potential source of anti-cancer agents and can improve the therapeutic efficacy of chemotherapy drugs. In this study, the role of TEMs in the synergistic anti-cancer effects of Fu-Zheng-Jie-Du ointment (FZJD) and 5-FU was evaluated.
Methods: The migration of TEMs was evaluated using the transwell assay. Tube formation assay and quantitative real-time polymerase chain reaction analysis were used to determine the pro-angiogenic activity of TEMs. Tumor-bearing mouse model and immunohistofluorescence stain were used to evaluate the anti-tumor effect of FZJD and the underlying mechanism.
Results: FZJD inhibited the migration and pro-angiogenic activity of TEMs. Additionally, tumor growth in the mice co-treated with FZJD and 5-FU was lower than that in the mice treated with FZJD or 5-FU. Immunohistofluorescence stain revealed that the migration of TEMs was not inhibited upon treatment with FZJD alone or in combination with 5-FU. Moreover, treatment with FZJD did not decrease the endothelial cell population. In contrast, the treatment combination of FZJD and 5-FU markedly decreased the endothelial cell population.
Conclusions: FZJD improves the anti-cancer efficacy of 5-FU through the inhibition of TEM-mediated angiogenesis.
Figure 1
Figure 2
Figure 3
Figure 4