Combined effects of Cantide and chemotherapeutic drugs on inhibition of tumor cells' growth in vitro and in vivo.
OBJECTIVE
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 micromol/L Cantide reduced the IC50 of DDP, 5-FU and ADM from 1.07, 4.15 and 0.29 microg/mL to 0.25, 1.52 and 0.12 microg/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 > or = 1.15) was observed at the lower concentration of DDP (< or = 1 microg/mL), 5-FU (< or = 10 microg/mL) and ADM (< or = 0.1 microg/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).


CONCLUSIONS
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.
Yang
Ying
Y
Beijing Institution of Radiation Medicine, Beijing 100850, China.
Lv
Qiu-Jun
QJ
Du
Qing-You
QY
Yang
Bing-Hu
BH
Lin
Ru-Xian
RX
Wang
Sheng-Qi
SQ
D000230:Adenocarcinoma / Q000188:drug therapy; D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology*; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy*; D002455:Cell Division / Q000187:drug effects; D045744:Cell Line, Tumor; D004357:Drug Synergism; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D008113:Liver Neoplasms / Q000188:drug therapy*; D008175:Lung Neoplasms / Q000188:drug therapy; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D020320:Oligoribonucleotides, Antisense / Q000494:pharmacology*; D054735:Phosphorothioate Oligonucleotides; D013274:Stomach Neoplasms / Q000188:drug therapy; D023041:Xenograft Model Antitumor Assays
D020320:Oligoribonucleotides, Antisense; D054735:Phosphorothioate Oligonucleotides; C478563:cantide