Arsenic sulfide inhibits cell migration and invasion of gastric cancer in vitro and in vivo.
Arsenic sulfide inhibits cell migration and invasion of gastric cancer in vitro and in vivo.
复制标题
硫化砷体内外抑制胃癌细胞迁移和侵袭的作用
DOI：
10.2147/dddt.s89805
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发表时间：
2015
期刊：
影响因子：
--
通讯作者：
Chen S
中科院分区：
文献类型：
--
作者：
Zhang L;Kim S;Ding W;Tong Y;Zhang X;Pan M;Chen S
我们以前研究发现硫化砷（As 4S 4）可诱导包括胃癌在内的几种人实体瘤细胞系的细胞周期阻滞和凋亡。本研究探讨了As 4S 4对胃癌细胞在体内外迁移和侵袭的影响。方法以人胃癌细胞株AGS和MGC 803为体外模型。采用创伤愈合迁移实验和Transwell侵袭实验检测As 4S 4对细胞迁移和侵袭的影响。采用蛋白质印迹法检测E-cadherin、β-catenin、Sp1、KLF 4和VEGF的表达。酶谱法检测MGC 803细胞中基质金属蛋白酶（MMP）-2和MMP-9的活性。通过接种MGC 803细胞建立小鼠异种移植模型，然后腹腔注射As 4S 4 3周，并监测体重和肿瘤变化。最后计算肿瘤生长抑制率，并采用免疫组化、Western blotting和实时荧光定量PCR检测肿瘤组织中与肿瘤侵袭转移相关的蛋白和基因的表达。结果As 4S 4能明显抑制胃癌细胞的迁移和侵袭能力。As 4S 4处理后，E-cadherin和KLF 4表达上调，β-catenin、VEGF和Sp1表达下调。As 4S 4可抑制MGC 803细胞中MMP-2和MMP-9的蛋白酶活性。同时，As 4S 4能有效抑制肿瘤的生长和侵袭能力。我们发现As 4S 4上调小鼠肿瘤组织中E-cadherin的表达，下调β-catenin、Sp1、VEGF和CD 34的表达，与体外结果一致。结论As 4S 4通过阻断肿瘤细胞粘附，降低肿瘤细胞破坏基底膜的能力，从而抑制肿瘤细胞的血管生成，抑制胃癌细胞的迁移和侵袭。
Background We previously showed that arsenic sulfide (As4S4) induced cell cycle arrest and apoptosis in several human solid tumor cell lines, including those of gastric cancer. In this study, we investigated the effect of As4S4 on the migration and invasion of gastric cancer cells both in vitro and in vivo. Methods The human gastric cancer cell lines AGS and MGC803 were selected as in vitro models. Wound-healing migration assay and Transwell invasion assay were carried out to determine the effects of As4S4 on cell migration and invasion. The expressions of E-cadherin, β-catenin, Sp1, KLF4, and VEGF were measured by Western blotting analysis. The activities of matrix metalloproteinase (MMP)-2 and MMP-9 in MGC803 cells were demonstrated by zymography assay. A mouse xenograft model was established by inoculation with MGC803 cells, then intraperitoneal injected with As4S4 for 3 weeks and monitored for body weight and tumor changes. Finally, the inhibition rate of tumor growth was calculated, and the expression of proteins and genes associated with tumor invasion and metastasis in tumor tissues were measured by immunohistochemistry, Western blotting, and real-time polymerase chain reaction assay. Results As4S4 significantly inhibited the migration and invasion of gastric cancer cell lines. The expression of E-cadherin and KLF4 was upregulated, while the expressions of β-catenin, VEGF, and Sp1 were downregulated following treatment with As4S4. Moreover, the protease activities of MMP-2 and MMP-9 were suppressed by As4S4 in MGC803 cells. Meanwhile, As4S4 effectively suppressed the abilities of tumor growth and invasion in the xenograft tumor model. We found that As4S4 upregulated the expression of E-cadherin and downregulated the expression of β-catenin, Sp1, VEGF, and CD34 in mouse tumor tissues, consistent with the results in vitro. Conclusion As4S4 inhibited the migration and invasion of gastric cancer cells by blocking tumor cell adhesion, decreasing the ability of tumor cells to destroy the basement membrane, and therefore suppressing their angiogenesis.
影响因子：
3.7
作者：
Tian Y;Liu Y;He P;Liu F;Zhou N;Cheng X;Shi L;Zhu H;Zhao J;Wang Y;Zhang M
通讯作者：
Zhang M