The important role of ADAM8 in the progression of hepatocellular carcinoma induced by diethylnitrosamine in mice
The important role of ADAM8 in the progression of hepatocellular carcinoma induced by diethylnitrosamine in mice
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ADAM8在二乙基亚硝胺诱导小鼠肝细胞癌进展中的重要作用
DOI：
10.1177/0960327114567767
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发表时间：
2015-11-01
影响因子：
2.8
通讯作者：
Han, H-M
中科院分区：
文献类型：
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作者：
Li, S-Q;Wang, D-M;Han, H-M
本研究旨在探讨去整合素和金属蛋白酶8(ADAM8)在肝细胞癌(HCC)发生发展中的具体作用。在二乙基亚硝胺诱导的小鼠肝癌形成过程中，分别在磷酸盐缓冲液中或磷酸盐缓冲液干预下，分别接种100g/100g L、200g/100L和300g/100L的抗腺相关黏附分子8的单抗。测定小鼠的存活率、体重和相对肝脏重量。第24周末检测小鼠血清天冬氨酸氨基转移酶(AST)、丙氨酸氨基转移酶(ALT)、甲胎蛋白(AFP)水平，苏木精-伊红染色，血管内皮生长因子A(VEGF-A)、增殖细胞核抗原(PCNA)、半胱氨酸天冬氨酸氨基转移酶3(Caspase 3)、B细胞白血病2(Bcl2)、B细胞白血病2相关X蛋白(Bax)、p53蛋白(P53)、ADAM8的表达水平。结果表明，抗ADAM8单抗干预有效地提高了小鼠的存活率，减轻了体重损失，增加了小鼠的肝脏相对重量，并呈剂量依赖关系(p<；0.05或p<；0.01)。抗ADAM8单抗干预还能显著降低小鼠血清AST、ALT和AFP水平(p<；0.05或p<；0.01)，延缓肝细胞癌的进展(p<；0.05或p<；0.01)，诱导Casp3、Bax和P53的表达(p<；0.05或p<；0.01)，抑制小鼠肝脏中VEGF-A、PCNA和bcl2的表达(p<；0.05或p<；0.01)。0.01)，与接受PBS干预的小鼠相比，呈剂量依赖性。我们的研究提示ADAM8可能通过调节这些因子的表达来促进肝细胞癌的进展。抗ADAM8单抗干预可能是一种潜在的肝癌治疗方法。
This study focuses on investigating the concrete role of a disintegrin and metalloproteinase 8 (ADAM8) in the progression of hepatocellular carcinoma (HCC). Mice received anti-ADAM8 monoclonal antibody (mAb) of 100 g/100 l, 200 g/100 l or 300 g/100 l, respectively, in phosphate-buffered saline (PBS) or PBS intervention during the progression of HCC induced by diethylnitrosamine. The survival rate, body weight, and relative liver weight were determined in the mice. Serum aspartate aminotransferase (AST), alanine aminotransferase (ALT) and -fetoprotein (AFP) level, hematoxylin-eosin staining, the expression level of vascular endothelial growth factor A (VEGF-A), proliferating cell nuclear antigen (PCNA), caspase 3 (Casp3), B cell leukemia 2 (Bcl2), B cell leukemia 2-associated X protein (Bax), protein p53 (P53), and ADAM8 were detected in the mice at the end of the 24th week. Our results showed that anti-ADAM8 mAb intervention effectively improved the survival rate, reduced the body weight loss and increased the relative liver weight in mice in a dose-dependent manner (p < 0.05 or p < 0.01). Anti-ADAM8 mAb intervention also significantly lowered serum AST, ALT, and AFP levels (p < 0.05 or p < 0.01), slowed the progression of HCC (p < 0.05 or p < 0.01), induced the expression of Casp3, Bax, and P53 (p < 0.05 or p < 0.01), and inhibited the expression of VEGF-A, PCNA, and Bcl2 in the liver of mice (p < 0.05 or p < 0.01) in a dose-dependent manner compared with the mice receiving PBS intervention. Our study suggested that ADAM8 might promote the progression of HCC by regulating the expression of these factors. Anti-ADAM8 mAb intervention might be suitable as a potential method for HCC therapy.