B7-H3 Promotes the Migration and Invasion of Human Bladder Cancer Cells via the PI3K/Akt/STAT3 Signaling Pathway.
B7-H3 Promotes the Migration and Invasion of Human Bladder Cancer Cells via the PI3K/Akt/STAT3 Signaling Pathway.
复制标题
B7-H3通过PI3K/Akt/STAT3信号通路促进人膀胱癌细胞的迁移和侵袭
DOI：
10.7150/jca.17759
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发表时间：
2017
影响因子：
3.9
通讯作者：
Gao Q
中科院分区：
文献类型：
--
作者：
Li Y;Guo G;Song J;Cai Z;Yang J;Chen Z;Wang Y;Huang Y;Gao Q
膀胱癌是最常见的恶性肿瘤之一。尽管已有研究发现B7-H3在人膀胱癌组织中异常表达，但B7-H3在膀胱癌中的确切作用及其分子机制尚不清楚。本研究首先检测了B7-H3在人膀胱癌标本和细胞系中的表达，并分析了其与临床病理参数的相关性。然后，将B7-H3的siRNAs或过表达载体导入T24或5637细胞，通过CCK-8、集落形成、流式细胞仪和Transwell检测细胞的增殖、凋亡、迁移和侵袭能力，Western blotting检测蛋白表达水平。结果表明，B7-H3在膀胱癌组织中表达上调，其表达水平与膀胱癌局部侵袭程度有关。B7-H3不影响细胞的增殖和凋亡，但通过对基质金属蛋白酶(MMP2/9)的调控改变了细胞的迁移和侵袭。B7-H3的敲除导致STAT3和PI3K/Akt通路活性降低，Akt是STAT3的上游调节因子。我们的结果提示，B7-H3的过表达通过PI3K/Akt/STAT3信号通路促进人膀胱癌细胞的迁移和侵袭。
Bladder cancer is one of most common malignant cancer. Although previous studies have found abnormal expression of B7-H3 in human bladder cancer tissues, the exact role and molecular mechanism of B7-H3 in bladder cancer remain unknown. In this study, we first detected the expression of B7-H3 in human bladder cancer samples and cell lines, and analyzed its correlations with clinicopathological pathological parameters. Next, siRNAs or overexpression plasmids of B7-H3 were transfected into T24 or 5637 cells, and cell proliferation, apoptosis, migration and invasion were analyzed via CCK-8, colony formation, flow cytometry and transwell assays, protein expression levels were determined by western blotting. The results presented here showed B7-H3 was upregulated in bladder cancer samples compared with normal tissues, and the expression level was correlated with local invasion status. B7-H3 did not affect cell proliferation and apoptosis, but cell migration and invasion were changed through the regulation of matrix metalloproteinase (MMP) 2/9. Knockdown of B7-H3 resulted in decreased activity of the STAT3 and PI3K/Akt pathways, and the Akt served as an upstream regulator of the STAT3. Our results suggest that the overexpression of B7-H3 promotes the migration and invasion of human bladder cancer cells through the PI3K/Akt/STAT3 signaling pathway.