Enhanced therapeutic effects of combined chemotherapeutic drugs and midkine antisense oligonucleotides for hepatocellular carcinoma

被引:15
作者
Dai, Li-Cheng [1 ]
Wang, Xiang
Yao, Xing
Lu, Yong-Liang
Ping, Jin-Liang
He, Jian-Fang
机构
[1] Huz Cent Hosp, Huzhou Key Lab Mol Med, Huzhou 313000, Zhejiang, Peoples R China
[2] Huz Cent Hosp, Dept Gen Surg, Huzhou 313000, Zhejiang, Peoples R China
[3] Huz Cent Hosp, Dept Pathol, Huzhou 313000, Zhejiang, Peoples R China
关键词
antisense oligonucleotide; midkine; carcinoma; hepatocellular; combination therapy;
D O I
10.3748/wjg.v13.i13.1989
中图分类号
R57 [消化系及腹部疾病];
学科分类号
摘要
AIM: To evaluate the effect of combined antisense oligonucleotides targeting midkine (MK-AS) and chemotherapeutic drugs [cisplatin(DDP), 5-fluorouracil (5-FU) and adriamycin (ADM)] on inhibition of HepG2 cell proliferation, and to analyze the efficacy of MK-AS used in combined ADM in in situ human hepatocellular carcinoma (HCC) model. METHODS: HepG2 cells were treated with MK-AS and/or chemotherapeutic drugs mediated by Lipofectin, and cell growth activity was determined by MTS assay. An in situ HCC model was used in this experiment. MK-AS, ADM and MK-AS + ADM were given intravenously for 20 d, respectively. The animal body weight and their tumor weight were measured to assess the effect of the combined therapy in vivo. RESULTS: Combined treatment with MK-AS reduced the IC50 of DDP, 5-FU and ADM in HepG2 cells. MK-AS significantly increased the inhibition rate of DDP, 5-FU and ADM. Additionally, synergism (Q 1.15) occurred at a lower concentration of ADM, 5-FU and DDP with combined MK-AS. Combined treatment with MK-AS and ADM resulted in the more growth inhibition on in situ human HCC model compared with treatment with chemotherapeutic drugs alone. CONCLUSION: MK-AS increases the chemosensitivity in HepG2 cells and in situ human HCC model, and the combination of MK-AS and ADM has a much better in vitro and in vivo synergism. (C) 2007 The WJG Press. All rights reserved.
引用
收藏
页码:1989 / 1994
页数:6
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