B7-H3 silencing inhibits tumor progression of mantle cell lymphoma and enhances chemosensitivity
B7-H3 silencing inhibits tumor progression of mantle cell lymphoma and enhances chemosensitivity
复制标题
B7-H3 沉默可抑制套细胞淋巴瘤的肿瘤进展并增强化疗敏感性。
DOI：
10.3892/ijo.2015.2962
复制
发表时间：
2015-06-01
影响因子：
5.2
通讯作者：
Ke, Xiaoyan
中科院分区：
文献类型：
--
作者：
Zhang, Wei;Wang, Yanfang;Ke, Xiaoyan
B7-H3（CD 276）是一种I型跨膜糖蛋白，属于B7免疫调节家族成员，在多种肿瘤中异常表达，与预后不良有关。然而，B7-H3在套细胞淋巴瘤（MCL）的肿瘤发生和化疗敏感性中的作用仍不清楚。我们确定下调B7-H3表达对套细胞淋巴瘤肿瘤进展和化疗药物敏感性的影响。分别在Maver和Z138套细胞淋巴瘤细胞系中使用慢病毒转导进行B7-H3敲低。采用CCK-8法、甲基纤维素集落形成法、PI染色法和Transwell体外实验研究B7-H3对细胞增殖、周期、迁移和侵袭的影响。通过建立Maver和Z138异种移植瘤模型，观察B7-H3对小鼠成瘤性的影响，免疫组化检测Ki-67和PCNA。B7-H3的下调在体外和体内显著降低MCL中的肿瘤增殖。在Maver和Z138异种移植模型的B7-H3敲低组中，肿瘤生长的平均抑制率分别为59.1%和65.0%（p=0.010和0.003），Ki-67和PCNA的表达均显著降低。B7-H3基因沉默后，Maver和Z138细胞周期均阻滞于G 0/G1期，细胞迁移率和侵袭能力下降。采用CCK-8和Annexin V-FITC/PI法检测B7-H3 RNAi对化疗药物抗肿瘤作用的影响。沉默B7-H3基因可增加Maver和Z138细胞对利妥昔单抗和苯达莫司汀的敏感性，并增强药物诱导的细胞凋亡。我们的研究首次证明B7-H3促进套细胞淋巴瘤的进展，B7-H3敲低显著增强化疗敏感性。这可能为套细胞淋巴瘤的治疗提供新的途径。
B7-H3 (CD276), known as a member of B7 immunoregulatory family, is a type I transmembrane glycoprotein aberrantly expressed in numerous types of cancer and associated with poor prognosis. However, the role of B7-H3 in oncogenesis and chemosensitivity of mantle cell lymphoma (MCL) remains unknown. We determined the effects of downregulating B7-H3 expression on tumor progression and the sensitivity of chemotherapeutic drug in mantle cell lymphoma. B7-H3 knockdown was performed using lentivirus transduction in the Maver and Z138 mantle cell lymphoma cell lines, respectively. The effects of B7-H3 on cell proliferation, cycle, migration and invasion were investigated by CCK-8 assay, methyl cellulose colony forming assay, PI staining, and Transwell assays in vitro. By establishing Maver and Z138 xenograft models, the effects of B7-H3 on tumorigenicity were observed, and Ki-67 and PCNA was detected by immunohistochemistry. The downregulation of B7-H3 significantly decreased tumor proliferation in MCL in vitro and in vivo. In the B7-H3 knockdown groups of Maver and Z138 xenograft models, the mean inhibition rate of tumor growth was 59.1 and 65.0% (p=0.010 and 0.003), and the expression of both Ki-67 and PCNA were significantly lower, respectively. After B7-H3 silencing, the cell cycles of Maver and Z138 were both arrested at G0/G1 phase, and the cell migration rates and invasion capacity were decreased as well. Moreover, the impacts of B7-H3 RNAi on the antitumor effect of chemotherapy drugs were determined with CCK-8 and Annexin V-FITC/PI assays in vitro and with xenograft models in vivo. The silencing of B7-H3 increased the sensitivity of Maver and Z138 cells to rituximab and bendamustine and enhanced the drug-induced apoptosis, respectively. Our study demonstrates for the first time that B7-H3 promotes mantle cell lymphoma progression and B7-H3 knockdown significantly enhances the chemosensitivity. This may provide a new therapeutic approach to mantle cell lymphoma.