Dai Li-Cheng, Wang Xiang, Yao Xing, Lu Yong-Liang, Ping Jin-Liang, He Jian-Fang
Huzhou Key Laboratory of Molecular Medicine, Huzhou Central Hospital, Huzhou 313000, Zhejiang Province, China.
World J Gastroenterol. 2007 Apr 7;13(13):1989-94. doi: 10.3748/wjg.v13.i13.1989.
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.
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.
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.
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.
评估靶向中期因子的反义寡核苷酸（MK-AS）与化疗药物[顺铂（DDP）、5-氟尿嘧啶（5-FU）和阿霉素（ADM）]联合应用对抑制HepG2细胞增殖的作用，并分析MK-AS联合ADM在人原位肝细胞癌（HCC）模型中的疗效。
用Lipofectin介导MK-AS和/或化疗药物处理HepG2细胞，采用MTS法测定细胞生长活性。本实验采用原位HCC模型。分别静脉给予MK-AS、ADM和MK-AS + ADM，持续20天。测量动物体重及其肿瘤重量，以评估联合治疗在体内的效果。
MK-AS联合治疗降低了DDP、5-FU和ADM对HepG2细胞的半数抑制浓度（IC50）。MK-AS显著提高了DDP、5-FU和ADM的抑制率。此外，较低浓度的ADM、5-FU和DDP与MK-AS联合时出现协同作用（协同指数Q为1.15）。与单独使用化疗药物相比，MK-AS和ADM联合治疗对人原位HCC模型的生长抑制作用更强。
MK-AS提高了HepG2细胞和人原位HCC模型的化疗敏感性，MK-AS与ADM联合具有更好的体外和体内协同作用。
