Ginsenoside Rg3 targets cancer stem cells and tumor angiogenesis to inhibit colorectal cancer progression  in vivo

There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

Abstract

Anti-angiogenic therapy has been successfully applied to treat colorectal cancer (CRC). Ginsenoside Rg3, derived from the Chinese herb ginseng, has anti-vascularization effects and can inhibit tumor growth and metastasis, and can sensitize cancer cells to chemotherapy. Therefore, in the present study, we investigated whether Rg3 could be appropriate for CRC treatment. Growth of CRC cells was assessed by an MTT (methyl thiazolyl tetrazolium) assay in vitro and using orthotopic xenograft models in vivo. mRNA expression was evaluated using real-time PCR. Protein levels were tested by western blotting, flow cytometry and immunohistochemistry. Migration was determined using a wound-healing assay. Stemness was further confirmed using a plate clone formation assay. We found that Rg3 repressed the growth and stemness of CRC cells both in vitro and in vivo. Rg3 also impaired the migration of CRC cells in vitro. Rg3 downregulated the expressions of angiogenesis-related genes, and repressed the vascularization of CRC xenografts. In addition, Rg3 strengthened the cytotoxicity of 5-Fluorouracil and oxaliplatin against orthotopic xenografts in vivo. Moreover, Rg3 downregulated the expressions of B7-H1 and B7-H3, high expressions of which were associated with reduced overall survival (OS) of CRC patients. Hence, Rg3 not only repressed the growth and stemness of CRC cells, but could also remodel the tumor microenvironment through repressing angiogenesis and promoting antitumor immunity. Therefore, Rg3 could be a novel therapeutic for the CRC treatment.

Related collections

Most cited references 37

Record: found
Abstract: found
Article: not found

Bevacizumab (Avastin), a humanized anti-VEGF monoclonal antibody for cancer therapy.

Napoleone Ferrara, Kenneth J Hillan, William E Novotny (2005)

Vascular endothelial growth factor (VEGF) is an endothelial cell-specific mitogen in vitro and an angiogenic inducer in vivo. The tyrosine kinases Flt-1 (VEGFR-1) and Flk-1/KDR (VEGFR-2) are high affinity VEGF receptors. VEGF plays an essential role in developmental angiogenesis and is important also for reproductive and bone angiogenesis. Substantial evidence also implicates VEGF as a mediator of pathological angiogenesis. Anti-VEGF monoclonal antibodies and other VEGF inhibitors block the growth of several tumor cell lines in nude mice. Clinical trials with VEGF inhibitors in a variety of malignancies are ongoing. Recently, a humanized anti-VEGF monoclonal antibody (bevacizumab; Avastin) has been approved by the FDA as a first-line treatment for metastatic colorectal cancer in combination with chemotherapy. Furthermore, VEGF is implicated in intraocular neovascularization associated with diabetic retinopathy and age-related macular degeneration.

0 comments Cited 239 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: found
Article: not found

The B7-H1 (PD-L1) T lymphocyte-inhibitory molecule is expressed in breast cancer patients with infiltrating ductal carcinoma: correlation with important high-risk prognostic factors.

Hazem Ghebeh, Shamayel Mohammed, Abeer Al-Omair … (2006)

B7-H1 molecule increases the apoptosis of tumor-reactive T lymphocytes and reduces their immunogenicity. Breast cancer is the second most common cause of mortality after lung cancer. Direct evidence linking B7-H1 with cancer has been shown in several malignancies; however, its expression in breast cancer has not been investigated. We used immunohistochemistry to investigate the expression of the B7-H1 molecule in 44 breast cancer specimens and to study its correlation with patients' clinicopathological parameters. The expression of B7-H1 was shown in 22 of 44 patients and was not restricted to the tumor epithelium (15 of 44, 34% in tumor cells), but was also expressed by tumor-infiltrating lymphocytes (TIL; 18 of 44, 41%). Interestingly, intratumor expression of B7-H1 was significantly associated with histologic grade III-negative (P = .012), estrogen receptor-negative (P = .036), and progesterone receptor-negative (P = .040) patients. In addition, the expression of B7-H1 in TIL was associated with large tumor size (P = .042), histologic grade III (P = .015), positivity of Her2/neu status (P = .019), and severe tumor lymphocyte infiltration (P = .001). Taken together, these data suggest that B7-H1 may be an important risk factor in breast cancer patients and may represent a potential immunotherapeutic target using monoclonal antibody against the B7-H1 molecule.

0 comments Cited 201 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: found
Article: not found

Prognostic significance of PD-L1 and PD-L2 in breast cancer.

Mauricio Z Baptista, Luis Sarian, Sophie F M Derchain … (2016)

PD-L1 and PD-L2 constitute an important antitumor immune response. In breast cancer, their prognostic value is still to be defined. In this study, we investigate the correlation between PD-L1 and PD-L2 protein expressions with clinical and pathologic features and disease-free survival and overall survival. To assess PD-L1 and PD-L2 expressions, we conducted immunohistochemistry studies using a breast cancer tissue microarray encompassing a total of 192 breast cancer cases, stages I, II, and III, with detailed clinical and outcome data. PD-L1 expression was present in 56.6% (107/189), and PD-L2 expression was identified in 50.8% (97/191) of breast cancer cases. Younger age at diagnosis, lymph node positivity, negative estrogen receptor, and recurrence at distant sites were all associated with both PD-L1 and PD-L2 expressions. The presence of larger tumors was associated only with PD-L1 expression. In our study, PD-L1 expression was significantly associated with better overall survival (P = .04) in breast cancer patients. Despite its association with poor clinical and pathologic features, PD-L1 expression emerges as a positive prognostic biomarker in breast cancer. This survival result might be due to the presence of a strong antitumor immune response leading to PD-L1 expression.

0 comments Cited 112 times – based on 0 reviews      Review now

Bookmark

All references

Author and article information

Journal

Journal ID (nlm-ta): Int J Oncol

Journal ID (iso-abbrev): Int. J. Oncol

Journal ID (publisher-id): IJO

Title: International Journal of Oncology

Publisher: D.A. Spandidos

ISSN (Print): 1019-6439

ISSN (Electronic): 1791-2423

Publication date Collection: January 2018

Publication date (Electronic): 01 November 2017

Publication date PMC-release: 01 November 2017

Volume: 52

Issue: 1

Pages: 127-138

Affiliations

[1 ]Department of Oncology

[2 ]Department of General Surgery and

[3 ]Department of Hematology, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215006

[4 ]PREMED Key Laboratory for Precision Medicine, Soochow University, Suzhou, Jiangsu 215021

[5 ]Center for Systems Biology, Soochow University, Suzhou, Jiangsu 215006

[6 ]Department of Pathology, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215006

[7 ]The Comprehensive Cancer Center, Suzhou Xiangcheng People's Hospital, Suzhou, Jiangsu 215000, P.R. China

Author notes

Correspondence to: Dr Wei Li or Dr Meng-Dan Xu, Department of Oncology, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215006, P.R. China, E-mail: liwei10@ 123456suda.edu.cn ; dr_weili@ 123456163.com , E-mail: doctor_xmd@ 123456163.com ; mengdanxu@ 123456suda.edu.cn

[*]

Contributed equally

Article

Publisher ID: ijo-52-01-0127

DOI: 10.3892/ijo.2017.4183

PMC ID: 5743384

PubMed ID: 29115601

SO-VID: ad444b0e-6d59-439b-8152-7c3cd8d8ae3d

License:

This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.

Ginsenoside Rg3 targets cancer stem cells and tumor angiogenesis to inhibit colorectal cancer progression in vivo

Read this article at

Abstract

Related collections

Karger: Oncology

Most cited references 37

Bevacizumab (Avastin), a humanized anti-VEGF monoclonal antibody for cancer therapy.

The B7-H1 (PD-L1) T lymphocyte-inhibitory molecule is expressed in breast cancer patients with infiltrating ductal carcinoma: correlation with important high-risk prognostic factors.

Prognostic significance of PD-L1 and PD-L2 in breast cancer.

Author and article information

Journal

Affiliations

Author notes

Article

History

Categories

Comments

Comment on this article

Similar content 884

Cited by 46

Most referenced authors 589