Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2022 Sep 12:2022:3919053.
doi: 10.1155/2022/3919053. eCollection 2022.

Therapeutic Effect of Curcumol on Chronic Atrophic Gastritis (CAG) and Gastric Cancer Is Achieved by Downregulating SDF-1 α/CXCR4/VEGF Expression

Xuehui Ma  1 , Zhengbo Zhang  2 , Xiayu Qin  1 , Lingjing Kong  1 , Wen Zhu  1 , Lingzhi Xu  3 , Xin Zhou  1
Affiliations

Therapeutic Effect of Curcumol on Chronic Atrophic Gastritis (CAG) and Gastric Cancer Is Achieved by Downregulating SDF-1 α/CXCR4/VEGF Expression

Xuehui Ma et al. J Oncol. .

Abstract

CAG is an essential procession of the transformation from gastritis into gastric cancer. A series of timely moves of diagnosis, treatment, and monitoring towards CAG to anticipate the potential population at risk of gastric cancer is an effective means to prevent gastric cancer occurrence. The main active monomer in Fuzheng Huowei Decoction is Curcumol, which is an indispensable ingredient in the treatment to CAG and gastric cancer. In this study, the CAG model, in vitro cultured gastric cancer cells, and participating nude mice were treated with Curcumol, and alterations in SDF-1α/CXCR4/VEGF expression were estimated using the assays of immunohistochemistry and Western blot. MTT, flow cytometry, transwell, HE staining, and tumor volume determination were applied for the verification of the regulatory effects of Curcumol on CAG and gastric cancer cells. The results showed that the expressions of VEGF, SDF-1α, CXCR4, and CD34 decreased in our CAG model with Curcumol treatment. Curcumol is in procession of an inhibitory effect toward the activity, migration, and invasion of gastric cancer cells, and it would also result in gastric cancer cells' apoptosis. We subsequently added SDF-1α overexpressing lentivirus to the Curcumol-treated group and found that the expressions of SDF-1α, CXCR4, and VEGF protein increased, and the inhibitory effect of Curcumol on gastric cancer cells was withdrawn. Our nude mouse experiment showed that Curcumol + SDF-1α group ended up with the largest tumor volume, while Fuzheng Huowei + NC group was with the smallest tumor volume. In conclusion, Curcumol is able to effectively protect the gastric tissue and suppress gastric cancer cells' viability. Curcumol functions as a therapeutic factor in chronic atrophic gastritis and gastric cancer by downregulating SDF-1α/CXCR4/VEGF expression.

PubMed Disclaimer

Conflict of interest statement

The authors declare that they have no conflicts of interest.

Figures

Figure 1
Figure 1
CAG model establishment and relevant detection. Tissue structures and marker protein expressions of CAG model animals were tested by HE staining and immunohistochemistry. N = 3, Scale bar: 50 μm.
Figure 2
Figure 2
Regulations of Curcumol on relevant protein expressions in CAG model. The expression levels of VEGF, SDF-1α, CXCR4, and CD34 in CAG model were assessed by immunohistochemistry. N = 3, Scale bar: 50 μm.
Figure 3
Figure 3
MTT determination on gastric cancer cell viability. N = 3.
Figure 4
Figure 4
Inhibitory effects of Curcumol on apoptosis, migration, and invasion of gastric cancer cells. (a) Flow cytometry determination on cell apoptosis. (b) Determination of Transwell assay on gastric cancer cell migration and invasion. (c) Determination of Western blot on the protein expression levels of SDF-1α, CXCR4, and VEGF in gastric cancer cells. N = 3, Scale bar: 50 μm.
Figure 5
Figure 5
Reversed effect of SDF-1α toward Curcumol's inhibition on gastric cancer cells. (a) Western blot detection on the protein expression levels of SDF-1α, CXCR4, and VEGF. (b) MTT detection on cell viability. (c) Flow cytometry detection on cellular apoptosis rate. (d) Detection of gastric cancer cell migration and invasion by Transwell test. N = 3, Scale bar: 50 μm.
Figure 6
Figure 6
Results of body weight and tumor volume in tumorigenesis test on nude mice. (a) Weight measurement results of nude mice. (b) Tumor volume detection results of nude mice. N = 6.
Figure 7
Figure 7
TUNEL and immunohistochemistry detection on apoptosis and protein expression of each group after treatment. N = 3, Scale bar: 50 μm.
See this image and copyright information in PMC

References

    1. Botezatu A., Bodrug N. Chronic atrophic gastritis: an update on diagnosis. Med Pharm Rep . 2021;94(1):7–14. doi: 10.15386/mpr-1887. - DOI - PMC - PubMed
    1. Holleczek B., Schottker B., Brenner H. Helicobacter pylori infection, chronic atrophic gastritis and risk of stomach and esophagus cancer: results from the prospective population-based ESTHER cohort study. International Journal of Cancer . 2020;146(10):2773–2783. doi: 10.1002/ijc.32610. - DOI - PubMed
    1. Zhang P., Yang M., Zhang Y., et al. Dissecting the single-cell transcriptome network underlying gastric premalignant lesions and early gastric cancer. Cell Reports . 2019;27(6):1934–1947.e5. doi: 10.1016/j.celrep.2019.04.052. - DOI - PubMed
    1. Pimentel-Nunes P., Libanio D., Marcos-Pinto R., et al. Management of epithelial precancerous conditions and lesions in the stomach (MAPS II): European society of gastrointestinal endoscopy (ESGE), European Helicobacter and microbiota study group (EHMSG), European society of pathology (ESP), and sociedade portuguesa de Endoscopia digestiva (SPED) guideline update 2019. Endoscopy . 2019;51(04):365–388. doi: 10.1055/a-0859-1883. - DOI - PubMed
    1. Lahner E., Zagari R. M., Zullo A., et al. Chronic atrophic gastritis: natural history, diagnosis and therapeutic management. A position paper by the Italian society of hospital gastroenterologists and digestive endoscopists [AIGO], the Italian society of digestive endoscopy [SIED], the Italian society of gastroenterology [SIGE], and the Italian society of internal medicine [SIMI] Digestive and Liver Disease . 2019;51(12):1621–1632. doi: 10.1016/j.dld.2019.09.016. - DOI - PubMed

LinkOut - more resources