Tian Si-Yuan, Chen Shou-Hua, Shao Bing-Feng, Cai Hong-Yu, Zhou Yuan, Zhou Yi-Long, Xu Ai-Bing
Department of Hepatic Oncology, Nantong Tumor Hospital Nantong, 226361, Jiangsu Province, China.
Department of Hepatic Surgery, Nantong Tumor Hospital Nantong, 226361, Jiangsu Province, China.
Int J Clin Exp Pathol. 2014 Jun 15;7(7):3752-62. eCollection 2014.
Leucine aminopeptidases (LAPs) were associated with tumor cell proliferation, invasion and/or angiogenesis. LAP3 is one important member of this family. However, its clinical significance and biological function in hepatocellular carcinoma (HCC) remains unknown. In the present study, we demonstrated that LAP3 expression was significantly up-regulated in HCC tissues as well as cells and was closely correlated with lower differentiation, positive lymph node metastasis and high Ki-67 expression, indicating a poor prognosis. Then cell viability assays, flow cytometry assays, wound-healing assays and matrigel invasion assays were performed to demonstrate that LAP3 promoted HCC cells proliferation by regulating G1/S checkpoint in cell cycle and advanced HCC cells migration. Furthermore, we discovered that knockdown LAP3 will enhance the sensitivity of HCC cells to cisplatin, thus promoting the cell death of HCC cells. Collectively, our results indicated that up-regulated expression of LAP3 might contribute to the proliferation and metastasis of HCC. Our data gains greater insight into the cancer-promoting role of LAP3 and its functions in HCC cells, possibly providing potential therapeutic strategies for clinical trials.
亮氨酸氨基肽酶(LAPs)与肿瘤细胞增殖、侵袭和/或血管生成相关。LAP3是该家族的一个重要成员。然而,其在肝细胞癌(HCC)中的临床意义和生物学功能仍不清楚。在本研究中,我们证明LAP3在HCC组织和细胞中表达显著上调,且与低分化、阳性淋巴结转移和高Ki-67表达密切相关,提示预后不良。然后进行细胞活力测定、流式细胞术测定、伤口愈合测定和基质胶侵袭测定,以证明LAP3通过调节细胞周期中的G1/S检查点促进HCC细胞增殖并促进HCC细胞迁移。此外,我们发现敲低LAP3会增强HCC细胞对顺铂的敏感性,从而促进HCC细胞死亡。总体而言,我们的结果表明LAP3表达上调可能促进HCC的增殖和转移。我们的数据更深入地了解了LAP3在促进癌症方面的作用及其在HCC细胞中的功能,可能为临床试验提供潜在的治疗策略。