黄芪多糖通过JAK/STAT3通路抑制口腔鳞癌SCC-25裸鼠移植瘤

邓力; 蔡婷; 王静雷; 夏雨; 周智

doi:10.13418/j.issn.1001-165x.2019.02.011

中国临床解剖学杂志 ›› 2019, Vol. 37 ›› Issue (2) : 169-173. DOI: 10.13418/j.issn.1001-165x.2019.02.011

实验研究

黄芪多糖通过JAK/STAT3通路抑制口腔鳞癌SCC-25裸鼠移植瘤

邓力，　蔡婷，　王静雷，　夏雨，　周智

作者信息 +

Astragalus polysaccharide inhibits oral squamous cell carcinoma cell line SCC-25 xenograft tumor by suppressing JAK/STAT3 signaling pathway

DENG Li, CAI Ting, WANG Jing-xue, XIA Yu, ZHOU Zhi

Author information +

文章历史 +

摘要

　目的　阐明黄芪多糖（AP）对口腔鳞癌（oral squamous cell carcinoma）细胞系SCC-25移植瘤模型小鼠的影响和机制。方法　皮下注射口腔鳞癌细胞系SCC-25建立异种移植瘤模型，将移植瘤BALB/c裸鼠模型随机分为4组：对照组（cTRL）、AP低剂量组（AP 10 mg）、AP中剂量组（AP 25 mg）和AP高剂量组（AP 50 mg）。AP治疗后，检测移植瘤体积和小鼠存活率；免疫组化检测Ki67和血管内皮生长因子（vascular endothelial growth factor，VEGF）表达水平；TUNEL实验检测移植瘤细胞凋亡情况；Western blot 检测JAK2/STAT3通路蛋白表达情况和磷酸化情况。结果　与对照组相比较，AP低、中、高剂量组肿瘤体积明显减小（P<0.01），小鼠存活率明显增加（P<0.01），Ki67和VEGF表达水平明显下降（P<0.01），JAK2/STAT3/c-myc磷酸化水平明显被抑制（P<0.01）。结论　AP以剂量依赖抑制SCC-25移植瘤体积，提高移植瘤小鼠存活率，下调Ki67和VEGF表达水平和JAK2/STAT3磷酸化水平。AP可能通过抑制JAK2/STAT3/c-myc信号通路抑制口腔鳞癌细胞SCC-25移植瘤生长。

Abstract

Objective　To elucidate the effect and mechanism of astragalus polysaccharide (AP) on SCC-25 xenograft tumor model mice in oral squamous cell carcinoma (OSCC) cell line.　Methods　The xenograft tumor model was established by subcutaneous injection of oral squamous cell carcinoma cell line SCC-25, and the xenograft tumor BALB/c nude mice models were randomly divided into 4 groups: a control group (cTRL), an AP low-dose group (AP 10 mg), an AP medium-dose group (AP 25 mg) and an AP high-dose group (AP 50 mg) for subsequent experiments. After treatment with AP, the tumor volume and survival rate of mice were measured. The expression of Ki67 and vascular endothelial growth factor (VEGF) were detected by immunohistochemistry. Apoptosis of xenograft tumor cells was detected by TUNEL assay. Protein expression of JAK2/STAT3 pathway members was detected by Western blot.　Results　Compared with the control group, the tumor volume of the low, medium and high-dose groups were decreased significantly (P<0.01), and the survival rate of the mice was increased significantly in AP treated groups (P<0.01). In addition, the expression levels of Ki67 and VEGF were decreased significantly (P<0.01), and the phosphorylation levels of JAK2/STAT3/c-myc were significantly inhibited (P<0.01).　Conclusion　AP inhibits the growth of SCC-25 xenograft tumors in a dose-dependent manner; particularly, AP increases the survival rate of xenograft tumor mice, and down-regulates the expression levels of Ki67 and VEGF and the phosphorylation level of JAK2/STAT3/c-myc. AP may inhibit oral squamous cell line SCC-25 xenograft tumor by inhibiting JAK2/STAT3/c-myc signaling pathway.

关键词

黄芪多糖 / 　口腔鳞癌 / 　移植瘤模型小鼠 / 　JAK2/STAT3

引用本文

EndNote

Ris (Procite)

Bibtex

导出引用

邓力,蔡婷,王静雷,夏雨,周智. 黄芪多糖通过JAK/STAT3通路抑制口腔鳞癌SCC-25裸鼠移植瘤[J]. 中国临床解剖学杂志. 2019, 37(2): 169-173 https://doi.org/10.13418/j.issn.1001-165x.2019.02.011

DENG Li, CAI Ting, WANG Jing-xue, XIA Yu, ZHOU Zhi. Astragalus polysaccharide inhibits oral squamous cell carcinoma cell line SCC-25 xenograft tumor by suppressing JAK/STAT3 signaling pathway[J]. Chinese Journal of Clinical Anatomy. 2019, 37(2): 169-173 https://doi.org/10.13418/j.issn.1001-165x.2019.02.011

参考文献

[1] Ferlay J, Soerjomataram I, Dikshit R, et al. Cancer incidence and mortality worldwide: sources, methods and major patterns in globocan 2012[J]. Int J Cancer, 2015, 136(5): E359-E386.
[2] Wang Y, Lu HL, Liu YD, et al. Cryptotanshinone sensitizes antitumor effect of paclitaxel on tongue squamous cell carcinoma growth by inhibiting the JAK/STAT3 signaling pathway[J]. Biomed pharmacother, 2017, 95: 1388-1396.
[3] Huang WH, Liao WR, Sun RX. Astragalus polysaccharide induces the apoptosis of human hepatocellular carcinoma cells by decreasing the expression of notch1[J]. Int J Mol Med, 2016, 38(2): 551-557.
[4] Jin M, Zhao K, Huang Q, et al. Structural features and biological activities of the polysaccharides from astragalus membranaceus[J]. Int J Biol Macromol, 2014, 64: 257-266.
[5] Guo L, Bai SP, Zhao L, et al. Astragalus polysaccharide injection integrated with vinorelbine and cisplatin for patients with advanced non-small cell lung cancer: effects on quality of life and survival[J]. Med Oncol, 2012, 29(3): 1656-1662.
[6] Deng LL, Zeng PY, Yue LL. Effects of astragalus polysaccharide on MICA gene expression in leukemia cell lines and NK cells cytotoxicity[J]. Zhonghua Xue Ye Xue Za Zhi, 2012, 33(9): 765-767.
[7] Li Q, Bao JM, Li XL, et al. Inhibiting effect of astragalus polysaccharides on the functions of CD4+CD25 hightreg cells in the tumor microenvironment of human hepatocellular carcinoma[J]. Chin Med J, 2012, 125(5): 786-793.
[8] Abbasi MM, Monfaredan A, Hamishehkar H, et al. New formulated "doxDOX-MTX-loaded nanoparticles" down- regulate HER2 gene expression and improve the clinical outcome in OSCCS model in rat: the effect of IV and oral modalities[J]. Asian Pac J Cancer Prev, 2014, 15(21): 9355-9360.
[9] Yin X, Chen L, Liu Y, et al. Enhancement of the innate immune response of bladder epithelial cells by astragalus polysaccharides through upregulation of TLR4 expression[J]. Biochem Biophys Res Commun, 2010, 397(2): 232-238.
[10]Liu X, Yang Y, Zhang X, et al. Compound astragalus and salvia miltiorrhiza extract inhibits cell invasion by modulating transforming growth factor-beta/smad in HEPG2 cell[J]. J Gastroenterol Hepatology, 2010, 25(2): 420-426.
[11]Na D, Liu FN, Miao ZF, et al. Astragalus extract inhibits destruction of gastric cancer cells to mesothelial cells by anti-apoptosis[J]. World J Gastroenterol, 2009, 15(5): 570-577.
[12]Tin MM, Cho CH, Chan K, et al. Astragalus saponins induce growth inhibition and apoptosis in human colon cancer cells and tumor xenograft[J]. Carcinogenesis, 2007, 28(6): 1347-1355.
[13]Bromberg J. Stat proteins and oncogenesis[J]. J Clin Invest, 2002,109(9): 1139-1142.
[14]Carpenter RL, Lo HW. STAT3 target genes relevant to human cancers[J]. Cancers, 2014, 6(2): 897-925.
[15]Masuda M, Wakasaki T, Suzui M, et al. STAT3 orchestrates tumor development and progression: the achilles' heel of head and neck cancers[J]. Curr Cancer Drug Targets, 2010, 10(1): 117-126.
[16]Oh HN, Seo JH, Lee MH, et al. Licochalcone C induced apoptosis in human oral squamous cell carcinoma cells by regulation of the JAK2/STAT3 signaling pathway[J]. J Cell Biochem, 2018, 119(12): 10118-10130.
[17]Peng HY, Cheng YC, Hsu YM, et al. Mpt0B098, a microtubule inhibitor, suppresses JAK2/STAT3 signaling pathway through modulation of SOCS3 stability in oral squamous cell carcinoma[J]. PloS One, 2016, 11(7): e0158440.
[18]Baral R, Patnaik S, Das BR. Co-overexpression of p53 and c-myc proteins linked with advanced stages of betel-and tobacco-related oral squamous cell carcinomas from eastern india[J]. Eur J Oral Sci, 1998, 106(5): 907-913.