Brief Reports
Copyright ©2005 Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Apr 28, 2005; 11(16): 2491-2496
Published online Apr 28, 2005. doi: 10.3748/wjg.v11.i16.2491
Combined effects of Cantide and chemotherapeutic drugs on inhibition of tumor cells’ growth in vitro and in vivo
Ying Yang, Qiu-Jun Lv, Qing-You Du, Bing-Hu Yang, Ru-Xian Lin, Sheng-Qi Wang
Ying Yang, Qiu-Jun Lv, Qing-You Du, Bing-Hu Yang, Ru-Xian Lin, Sheng-Qi Wang, Beijing Institution of Radiation Medicine, Beijing 100850, China
Ying Yang, Department of Biochemistry, National Institute for the Control of Pharmaceutical and Biological Product, Beijing 100050, China
Author contributions: All authors contributed equally to the work.
Supported by the National Nature Science Foundation of China, No. 39870879, and Key Technologies R and D Program of China, No. 2002AA2Z3337
Correspondence to: Professor Sheng-Qi Wang, Beijing Institution of Radiation Medicine, Beijing 100850, China. sqwang@nic.bmi.ac.cn
Telephone: +86-10-66932211 Fax: +86-10-66932211
Received: March 31, 2004
Revised: April 2, 2004
Accepted: May 29, 2004
Published online: April 28, 2005
Abstract

AIM: To investigate the combination effect of hTERT antisense oligonucleotide “Cantide” and three chemotherapeutic drugs (cisplatin, 5-fluorouracil (5-FU) and adriamycin (ADM)) on inhibiting the proliferation of HepG2, BGC and A549 cell lines in vitro, and to investigate the efficacy of Cantide used in combination with cisplatin (DDP) in vivo.

METHODS: Cantide was transfected into these tumor cells by Lipofectin, and cell growth activity was calculated by microcytotoxicity assay. In vivo study, cells of HepG2 were implanted in Balb/c nude mice for 4 d. Then Cantide, DDP and Cantide+DDP were given intraperitoneally for 24 d respectively. The body weights of the tumor-bearing animals and their tumor mass were measured later to assess the effect of combination therapy in the nude mice. To evaluate the interaction of Cantide and these chemotherapeutic drugs, SAS software and Jin Zhengjun method were used.

RESULTS: Combination treatments with 0.1 μmol/L Cantide reduced the IC50 of DDP, 5-FU and ADM from 1.07, 4.15 and 0.29 μg/mL to 0.25, 1.52 and 0.12 μg/mL respectively. The inhibition ability of DDP, 5-FU and ADM respectively in combination with Cantide in these tumor cells was higher than that of these drugs alone (P<0.0001). And synergism (Q≥1.15) was observed at the lower concentration of DDP (≤1 μg/mL), 5-FU (≤10 μg/mL) and ADM (≤0.1 μg/mL) with combination of Cantide. In vivo, combination treatment with Cantide and DDP produced the greater growth inhibition of human liver carcinoma cells HepG2 in nude mice (0.65±0.19 g tumor) compared with that when only one of these drugs was used (Cantide group: 1.05±0.16 g tumor, P = 0.0009<0.001; DDP group: 1.13±0.09 g tumor, P = 0.0001<0.001).

CONCLUSION: These findings indicate that Cantide may enhance therapeutic effectiveness of chemotherapeutic drugs over a wide range of tumor cells in vitro, and the combination use of Cantide and DDP can produce much higher inhibition rates, as compared with when either of these drugs was used only in vivo.

Keywords: hTERT; Antisense oligonucleotide; Tumor; Chemotherapeutic drugs