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
. 2019 Mar 26:12:2225-2234.
doi: 10.2147/OTT.S197816. eCollection 2019.

Effect of Th9/IL-9 on the growth of gastric cancer in nude mice

Li Cai  1 , Yue Zhang  2 , Yifei Zhang  3 , Hongbing Chen  3 , Jinchen Hu  3
Affiliations

Effect of Th9/IL-9 on the growth of gastric cancer in nude mice

Li Cai et al. Onco Targets Ther. .

Abstract

Objective: By neutralizing IL-9 in a nude mouse model, the study aimed to investigate the role of Th9/IL-9 on the growth of gastric cancer in mice.

Materials and methods: Male BALB/c nude mice were randomly divided into three groups: a normal control group (Control), an SGC-7901 xenografted nude mice model group (Model), and a rIL-9 treatment group (Treat). The weight of the tumors was recorded to calculate the tumor inhibition rate. Flow cytometry was used to detect the cell frequency of Th9, Th17, and Treg in peripheral blood. The IL-4, IL-9, IL-10, IL-25, VEGF, and TGF-β levels in serum were determined by ELISA. The cellular migration and invasion were investigated by transwell assay. Immunohistochemical and Western blot were used to detect the expression of IL-9, CD34, PU.1, p53, and p21 proteins in gastric cancer tissue. The mRNA expression levels of IL-9, IL-21, and PU.1 in gastric cancer tissue were determined by qRT-PCR.

Result: rIL-9 can significantly inhibit the growth of gastric cancer. The frequency of Th9, Th17, and Treg in peripheral blood was decreased upon treatment. The levels of IL-4, IL-9, IL-10, IL-25, VEGF, and TGF-β in serum were significantly reduced in the Treat group compared with the Model group (P<0.05). rIL-9 can inhibit cellular migration and invasion and reduce the mRNA level of IL-9, IL-21, and PU.1. Meanwhile, in the Treat group, the expression of IL-9, CD34, and PU.1 was significantly reduced, whereas the expression of p53 and p21 was significantly increased compared with the Model group (P<0.05).

Conclusion: This study suggested that Th9/IL-9 has a deleterious role in gastric cancer.

Keywords: CD4 T lymphocyte; IL-9; Th9; gastric cancer.

PubMed Disclaimer

Conflict of interest statement

Disclosure The authors declare no conflicts of interest in this work.

Figures

Figure 1
Figure 1
Effect of rIL-9 on tumor growth in SGC-7901-xenografted nude mice, rIL-9 inhibited the tumor volume (A, B) and average tumor weight (C) in SGC-7901-xenografted nude mice. Data were shown as mean±SD. #P<0.05 vs model group.
Figure 2
Figure 2
Effect of rIL-9 on the cell frequency of Th9, Th17, and Treg in peripheral blood of SGC-7901-xenografted nude mice (A). rIL-9 inhibited the cell frequency of Th9, Th17, and Treg in peripheral blood of SGC-7901-xenografted nude mice (B). Notes: Data are shown as mean±SD. *P<0.05 vs Control group, #P<0.05 vs Model group.
Figure 3
Figure 3
Effect of rIL-9 on the factors in serum of SGC-7901-xenografted nude mices. rIL-9 could inhibit the levels of IL-4 (A), IL-9 (B), IL-10 (C), IL-25 (D), VEGF (E), and TGF-β (F) in serum of SGC-7901-xenografted nude mice. Notes: Data are shown as mean±SD. *P<0.05 vs Control group, #P<0.05 vs Model group.
Figure 4
Figure 4
Effect of rIL-9 on the migration and invasion of SGC-7901 cell (A). IL-9 can promote tumor migration (B) and invasion (C) (400×). Data were shown as mean±SD. #P<0.05 vs model group.
Figure 5
Figure 5
Effect of rIL-9 on the expression of IL-9 and CD34 proteins in gastric cancer tissue (A). rIL-9 could inhibit the expression of IL-9 (B) and CD34 (C). Notes: Data are shown as mean±SD. #P<0.05 vs Model group.
Figure 6
Figure 6
Effect of rIL-9 on the mRNA expression of IL-9, IL-21, and PU.1 in gastric cancer tissue. rIL-9 can inhibit the mRNA expression of IL-9, IL-21, and PU.1. Notes: Data are shown as mean±SD. #P<0.05 vs Model group.
Figure 7
Figure 7
Effect of rIL-9 on the expression of PU.1, p53, and p21 proteins in gastric cancer tissue (A). rIL-9 can reduce the expression of PU.1 and increase the expression of p53 and p21 (B). Notes: Data are shown as mean±SD. #P<0.05 vs Model group.
See this image and copyright information in PMC

References

    1. Siegel R, Ma J, Zou Z, Jemal A. Cancer statistics, 2014. CA Cancer J Clin. 2014;64(1):9–29. doi: 10.3322/caac.21208. - DOI - PubMed
    1. Elimova E, Shiozaki H, Wadhwa R, et al. Medical management of gastric cancer: a 2014 update. World J Gastroenterol. 2014;20(38):13637–13647. doi: 10.3748/wjg.v20.i38.13637. - DOI - PMC - PubMed
    1. Tsutani Y, Yoshida K, Sanada Y, et al. Decreased orotate phosphoribo-syltransferase activity produces 5-fluorouracil resistance in a human gastric cancer cell line. Oncol Rep. 2008;20(6):1545–1551. - PubMed
    1. Sakuramoto S, Sasako M, Yamaguchi T, et al. ACTS-GC Group Adju-vant chemotherapy for gastric cancer with S-1, an oral fluoropyrimidine. N Engl J Med. 2007;357(18):1810–1820. doi: 10.1056/NEJMoa072252. - DOI - PubMed
    1. Huang D, Yang Y, Zhang S, et al. Regulatory T-cell density and cytotoxic T lymphocyte density are associated with complete response to neoad-juvant paclitaxel and carboplatin chemoradiotherapy in gastric cancer. Exp Ther Med. 2018;16(5):3813–3820. doi: 10.3892/etm.2018.6684. - DOI - PMC - PubMed