CoChat
Sign Up
Cited by 7Curcumin's Biomedical ApplicationsRadiation Therapy and DosimetryNanoplatforms for cancer theranostics

The DOI matches its Crossref record; 36 of the 36 references it cites were found in a registry or an index.

Curcumin Administered in Combination with Glu-GNPs Induces Radiosensitivity in Transplanted Tumor MDA-MB-231-luc Cells in Nude Mice

Open access
Li, Mengjie, Lin, Ling, Guo, Tingting, Wu, Yujian, Lin, Jiayi, Liu, Yuanyuan, Yang, Ke, Hu, Chenxia·2021·BioMed Research International
DOI 10.1155/2021/9262453PMC PMC8610687
Open this paper in CoChat — free accountOpen PDF

Abstract

Curcumin is a type of plant polyphenol extracted from Curcuma longa L. rhizome, which demonstrates antitumor activity in breast cancer cells in vitro. To investigate the combined effect and possible mechanism of curcumin and glucose‐gold nanoparticles (Glu‐GNPs), the radiosensitivity of breast carcinoma xenografts was assessed in nude mice. MDA-MB-231 cells labeled with firefly luciferase were inoculated into the mammary fatty pads of nude mice to establish a transplantation tumor model of human breast cancer. The tumor‐bearing mice were treated with different drugs (curcumin, Glu‐GNPs, and cisplatin) for 3 weeks prior to radiotherapy. The body weights and tumor volumes of the mice were measured in regular intervals. Tumor bioluminescence intensity was determined in real‐time using an in vivo bioluminescence imaging system to monitor tumor growth. Transplanted tumor tissue samples were taken for hematoxylin and eosin (HE) staining, and the expression of VEGF, HSP90, HIF‐1α, and MMP9 was evaluated via reverse transcription‐quantitative PCR or immunohistochemistry. The results revealed that the breast tumor‐bearing nude mouse model was successfully established, as evidenced by a stable expression of luciferase. Curcumin inhibited the growth of tumors without causing significant weight loss in mice. Furthermore, additive inhibition was demonstrated when curcumin was administered in combination with Glu‐GNPs and irradiation. Tumor bioluminescence intensity was decreased in the model group following curcumin, Glu‐GNPs, and irradiation treatment. HE staining demonstrated that transplanted tumors were malignant, with necrotic tissue exhibited centrally. It was concluded that curcumin administered in combination with Glu‐GNPs and X‐ray irradiation could reduce the protein expression of VEGF, HSP90, HIF‐1α, and MMP9 in tumor tissue when compared with the model group. Curcumin and Glu‐GNPs administered with X‐ray irradiation significantly inhibited tumor growth and induced radiosensitivity, which may be associated with the inhibition of angiogenesis in tumor tissue.

Overview

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1155/2021/9262453

Cites

36 of 36 references verified0 citation errors · 0 not checkable

Statistics

Figures

Figure 1 Cell culture and model establishment. (a) MDA-MB-231-luc cells were imaged (magnification, ×100; scale bar, 5 μm). (b) The bioluminescence intensity of different numbers of cells (1.25 × 104, 2.5 × 104, and 5 × 104) was detected using an in vivo imaging system in a black opaque 96-well plate. (c) A breast tumor-bearing mouse model exhibiting stable luciferase expression was successfully established 3-7 days after inoculation. (d) Schematic diagram of xenografts in nude mice. MDA-MB-231-luc cells were transplanted into the second pair of subcutaneous mammary glands on the left-hand side. When the tumor volume reached 100-200 mm3, curcumin in corn oil (2% DMSO), Glu-GNPs, and cisplatin in saline solution were administrated regularly. After 3 weeks of treatment, tumor-bearing mice (IR, Glu-GNPs+IR, Cur+IR, and Cur+Glu-GNPs+IR) were treated with irradiation (10 Gray). After further 3 days, the fluorescence intensity of mice in each group was detected using the in vivo imaging system. Glu-GNPs: glucose-gold nanoparticles; IR: irradiation; Cur: curcumin.
Figure 1 Cell culture and model establishment. (a) MDA-MB-231-luc cells were imaged (magnification, ×100; scale bar, 5 μm). (b) The bioluminescence intensity of different numbers of cells (1.25 × 104, 2.5 × 104, and 5 × 104) was detected using an in vivo imaging system in a black opaque 96-well plate. (c) A breast tumor-bearing mouse model exhibiting stable luciferase expression was successfully established 3-7 days after inoculation. (d) Schematic diagram of xenografts in nude mice. MDA-MB-231-luc cells were transplanted into the second pair of subcutaneous mammary glands on the left-hand side. When the tumor volume reached 100-200 mm3, curcumin in corn oil (2% DMSO), Glu-GNPs, and cisplatin in saline solution were administrated regularly. After 3 weeks of treatment, tumor-bearing mice (IR, Glu-GNPs+IR, Cur+IR, and Cur+Glu-GNPs+IR) were treated with irradiation (10 Gray). After further 3 days, the fluorescence intensity of mice in each group was detected using the in vivo imaging system. Glu-GNPs: glucose-gold nanoparticles; IR: irradiation; Cur: curcumin.CC BY · PubMed Central
Figure 2 Tumor growth was decreased after treatment (n = 5). (a) Tumor volumes were measured every 4 days. (b) The weight of nude mice was measured weekly. (c) Images of transplanted tumor tissues which were removed after treatment and (d) weighed. Data were normalized to that of the model group, and data were presented as the mean ± SD. ∗P < 0.05, ∗∗P < 0.01, and ∗∗∗P < 0.001 vs. the model group (Student's t-test).
Figure 2 Tumor growth was decreased after treatment (n = 5). (a) Tumor volumes were measured every 4 days. (b) The weight of nude mice was measured weekly. (c) Images of transplanted tumor tissues which were removed after treatment and (d) weighed. Data were normalized to that of the model group, and data were presented as the mean ± SD. ∗P < 0.05, ∗∗P < 0.01, and ∗∗∗P < 0.001 vs. the model group (Student's t-test).CC BY · PubMed Central
Figure 3 Bioluminescence intensity following in vivo imaging. (a) After treatment, the bioluminescence intensity of tumor-bearing mice that were intraperitoneally injected with luciferase substrate (150 mg/kg) was monitored using an in vivo imaging system (color). Mice were anesthetized by inhaling isoflurane. Bioluminescence was observed under the same conditions. (b) The bioluminescence intensity of each group was quantified.
Figure 3 Bioluminescence intensity following in vivo imaging. (a) After treatment, the bioluminescence intensity of tumor-bearing mice that were intraperitoneally injected with luciferase substrate (150 mg/kg) was monitored using an in vivo imaging system (color). Mice were anesthetized by inhaling isoflurane. Bioluminescence was observed under the same conditions. (b) The bioluminescence intensity of each group was quantified.CC BY · PubMed Central
Figure 4 Detection of tumor tissue samples. (a) Representative images of HE staining (magnification, ×400) depicting the degree of malignancy in xenografts and tumor cells. The cells of tumor tissues exhibited large and dark nuclei with almost no cytoplasm and centrally located necrosis. Arrows indicate tumor cells (scale bars, 20 μm). RT-qPCR analyses of (b) HSP90 and (c) VEGF mRNA levels in tumor tissue. β-Actin was used as a reference gene. Data were presented as the mean ± SD of three independent experiments. ∗P < 0.05 vs. the model group (Student's t-test). (d) Representative images of HSP90 and VEGF IHC staining (magnification, ×400). Tumor tissue was immunostained using DAB (brown) and hematoxylin (blue) for nuclear counterstaining. Arrows indicate the nuclear expression of HSP90 or VEGF in breast cancer cells (scale bars, 20 μm). (e) The semiquantitative scoring analysis of HSP90 and (f) VEGF protein expression in tumor tissue. HE: hematoxylin and eosin; HSP90: heat shock protein 90.
Figure 4 Detection of tumor tissue samples. (a) Representative images of HE staining (magnification, ×400) depicting the degree of malignancy in xenografts and tumor cells. The cells of tumor tissues exhibited large and dark nuclei with almost no cytoplasm and centrally located necrosis. Arrows indicate tumor cells (scale bars, 20 μm). RT-qPCR analyses of (b) HSP90 and (c) VEGF mRNA levels in tumor tissue. β-Actin was used as a reference gene. Data were presented as the mean ± SD of three independent experiments. ∗P < 0.05 vs. the model group (Student's t-test). (d) Representative images of HSP90 and VEGF IHC staining (magnification, ×400). Tumor tissue was immunostained using DAB (brown) and hematoxylin (blue) for nuclear counterstaining. Arrows indicate the nuclear expression of HSP90 or VEGF in breast cancer cells (scale bars, 20 μm). (e) The semiquantitative scoring analysis of HSP90 and (f) VEGF protein expression in tumor tissue. HE: hematoxylin and eosin; HSP90: heat shock protein 90.CC BY · PubMed Central
Figure 5 The protein expressions of MMP9 and HIF-1α in tumor tissue samples by immunohistochemistry. (a) Representative images of MMP9 and (b) HIF-1α IHC staining (magnification, ×200). Tumor tissue was immunostained using DAB (brown) and hematoxylin (blue) for nuclear counterstaining. Arrows indicate the nuclear expression of MMP9 or HIF-1α in breast cancer cells (scale bars, 100 μm). (c) The semiquantitative scoring analysis of MMP9 and (d) HIF-1α protein expression in tumor tissue. IHC: immunohistochemistry; MMP9: matrix metalloprotein-9; HIF-1α: hypoxia-inducible factor-1α.
Figure 5 The protein expressions of MMP9 and HIF-1α in tumor tissue samples by immunohistochemistry. (a) Representative images of MMP9 and (b) HIF-1α IHC staining (magnification, ×200). Tumor tissue was immunostained using DAB (brown) and hematoxylin (blue) for nuclear counterstaining. Arrows indicate the nuclear expression of MMP9 or HIF-1α in breast cancer cells (scale bars, 100 μm). (c) The semiquantitative scoring analysis of MMP9 and (d) HIF-1α protein expression in tumor tissue. IHC: immunohistochemistry; MMP9: matrix metalloprotein-9; HIF-1α: hypoxia-inducible factor-1α.CC BY · PubMed Central

Verification

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Citations

Cites

1 retracted

Show all 36 references

Cited by

Sorted by citations

Related

See all

Metadata

Authors
Li, M., Lin, L., Guo, T., Wu, Y., Lin, J., Liu, Y., Yang, K., & Hu, C.
Affiliations
Guangzhou University of Chinese Medicine (CN)
Corresponding author
Hu, Chenxia
ORCID
Venue
BioMed Research International
Publisher
Wiley
Published
2021-01
Volume
2021
Issue
1
Pages
9262453-9262453
ISSN
  • 1110-7243 (ISSN-L)
  • 2314-6133
  • 2314-6141
DOI
10.1155/2021/9262453
PMC
PMC8610687
OpenAlex
W3211849558
Cited by
7
References
36
Citations by year
2026: 1 · 2024: 4 · 2022: 2
FWCI
0.48
Type
journal article
Language
en
Open access
Licence
Locations
  • BioMed Research International (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
National Natural Science Foundation of China (81873052, 81503301)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Medicine › Curcumin's Biomedical Applications
  • Physical Sciences › Physics and Astronomy › Radiation › Radiation Therapy and Dosimetry
  • Physical Sciences › Engineering › Biomedical Engineering › Nanoplatforms for cancer theranostics
Keywords
curcumin, radiosensitization, breast cancer, MDA-MB-231 cells, xenograft tumor model, angiogenesis inhibition, vascular endothelial growth factor, HIF-1α, HSP90, MMP-9, combination therapy, X-ray irradiation, cisplatin
MeSH terms
Animals, Antineoplastic Agents, Phytogenic, Breast Neoplasms, Combined Modality Therapy, Curcumin, Female, Glucose, Gold, Humans, Mice, Inbred BALB C, Mice, Nude, Neovascularization, Pathologic, Radiation Tolerance, Radiation-Sensitizing Agents, RNA, Messenger, HSP90 Heat-Shock Proteins, Matrix Metalloproteinase 9, Xenograft Model Antitumor Assays, Vascular Endothelial Growth Factor A, Cell Line, Tumor, Mice, Hypoxia-Inducible Factor 1, alpha Subunit, Metal Nanoparticles

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review