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Copyright ©2007 Baishideng Publishing Group Co., Limited. All rights reserved.
World J Gastroenterol. Apr 7, 2007; 13(13): 1989-1994
Published online Apr 7, 2007. doi: 10.3748/wjg.v13.i13.1989
Enhanced therapeutic effects of combined chemotherapeutic drugs and midkine antisense oligonucleotides for hepatocellular carcinoma
Li-Cheng Dai, Xiang Wang, Xing Yao, Yong-Liang Lu, Jin-Liang Ping, Jian-Fang He
Li-Cheng Dai, Xiang Wang, Jian-Fang He, Huzhou Key Laboratory of Molecular Medicine, Huzhou Central Hospital, Huzhou 313000, Zhejiang Province, China
Xing Yao, Yong-Liang Lu, Department of General Surgery, Huzhou Central Hospital, Huzhou 313000, Zhejiang Province, China
Jin-Liang Ping, Department of Pathology, Huzhou Central Hospital, Huzhou 313000, Zhejiang Province, China
Author contributions: All authors contributed equally to the work.
Supported by grants from the Zhejiang Province Medicine and Health Research Fund, No. 2003A077 and Huzhou Natural Science Foundation, No. 2004SZX07-11, China
Correspondence to: Li-Cheng Dai, Professor, Huzhou Key Laboratory of Molecular Medicine, Huzhou Central Hospital, Huzhou 313000, Zhejiang Province, China. dlc@hzhospital.com
Telephone: +86-572-2033020 Fax: +86-572-2033020
Received: January 11, 2007
Revised: February 10, 2007
Accepted: March 15, 2007
Published online: April 7, 2007
Abstract

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.

Keywords: Antisense oligonucleotide, Midkine, Carci-noma, Hepatocellular, Combination therapy