title: B7-H3 silencing inhibits tumor progression of mantle cell lymphoma and enhances chemosensitivity.
abstract: 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.
authors: Department of Hematology and Lymphoma Research Center, Peking University Third Hospital, Beijing 100191, P.R. China.
authors: Wei
authors: W
authors: Zhang
authors: Department of Hematology and Lymphoma Research Center, Peking University Third Hospital, Beijing 100191, P.R. China.
authors: Yanfang
authors: Y
authors: Wang
authors: Department of Hematology and Lymphoma Research Center, Peking University Third Hospital, Beijing 100191, P.R. China.
authors: Jing
authors: J
authors: Wang
authors: Department of Hematology and Lymphoma Research Center, Peking University Third Hospital, Beijing 100191, P.R. China.
authors: Fei
authors: F
authors: Dong
authors: Department of Hematology and Lymphoma Research Center, Peking University Third Hospital, Beijing 100191, P.R. China.
authors: Mingxia
authors: M
authors: Zhu
authors: Department of Hematology and Lymphoma Research Center, Peking University Third Hospital, Beijing 100191, P.R. China.
authors: Wenli
authors: W
authors: Wan
authors: Department of Hematology and Lymphoma Research Center, Peking University Third Hospital, Beijing 100191, P.R. China.
authors: Haishen
authors: H
authors: Li
authors: Department of Hematology and Lymphoma Research Center, Peking University Third Hospital, Beijing 100191, P.R. China.
authors: Feifei
authors: F
authors: Wu
authors: Department of Hematology and Lymphoma Research Center, Peking University Third Hospital, Beijing 100191, P.R. China.
authors: Xinxing
authors: X
authors: Yan
authors: Department of Hematology and Lymphoma Research Center, Peking University Third Hospital, Beijing 100191, P.R. China.
authors: Xiaoyan
authors: X
authors: Ke
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000494:pharmacology; D017209:Apoptosis; D060887:B7 Antigens / Q000235:genetics / Q000378:metabolism*; D000069461:Bendamustine Hydrochloride / Q000008:administration & dosage* / Q000494:pharmacology; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D018450:Disease Progression; D005260:Female; D020868:Gene Silencing; D006801:Humans; D020522:Lymphoma, Mantle-Cell / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D051379:Mice; D009374:Neoplasms, Experimental; D000069283:Rituximab / Q000008:administration & dosage* / Q000494:pharmacology
chemical_list: D000970:Antineoplastic Agents; D060887:B7 Antigens; C423237:CD276 protein, human; D000069283:Rituximab; D000069461:Bendamustine Hydrochloride