Inhibition of tumor growth and metastasis with antisense oligonucleotides (Cantide) targeting hTERT in an in situ human hepatocellular carcinoma model.

Abstract

AIM:

To evaluate the in vivo antitumor effects of Cantide and the combined effect with 5-fluorouracil.

METHODS:

An in situ human hepatocellular carcinoma model was established in mice livers orthotopically. Drugs were administered intravenously and tumor sizes were monitored with calipers. Plasma alpha-fetoprotein(AFP) were detected by radiation immunoassay. Morphology of tumors was evaluated by hematoxylin-eosin (H and E) staining of histological sections. Human telomerase reverse transcriptase (hTERT) protein levels were detected by Western blotting.

RESULTS:

Cantide significantly inhibit in situ human hepatocellular carcinoma growth in mice with a 75 and 50 mg.kg(-1).d(-1) administration of Cantide compared to the saline group in a dose-dependent manner, which included injecting Cantide 25 mg.kg(-1).d(-1) by iv for 20 d after surgically removing the tumor in liver. Cantide was also found to prevent tumor recurrence in the liver and metastasis in the lung, showing a dose-dependent response. When Cantide was administered by iv combined with 5-fluorouracil, it resulted in a significant reduction in tumor growth compared to either agent alone treatment group. After the treatment with Cantide alone or combined with 5-fluorouracil, plasma AFP concentration decreased in a dose-dependent manner.

CONCLUSION:

These results demonstrated that Cantide was an effective antitumor antisense oligonucleotide in vivo and has the potential to be developed into a clinical anti-cancer drug.

• Authors: Ru-xian Lin, Chao-wei Tuo, Qiu-jun Lü, Wei Zhang, Sheng-qi Wang
• Journal: Acta pharmacologica Sinica (Acta Pharmacol Sin) Vol. 26 Issue 6 Pg. 762-8 (Jun 2005) ISSN: 1671-4083 [Print] United States
• PMID: 15916744 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents
• DNA-Binding Proteins
• Oligoribonucleotides, Antisense
• Phosphorothioate Oligonucleotides
• alpha-Fetoproteins
• cantide
• Telomerase
• Fluorouracil

Topics

• Animals
• Antineoplastic Agents (administration & dosage, pharmacology)
• Carcinoma, Hepatocellular (blood, pathology)
• Cell Line, Tumor
• DNA-Binding Proteins (genetics)
• Dose-Response Relationship, Drug
• Drug Synergism
• Female
• Fluorouracil (pharmacology)
• Humans
• Liver (pathology)
• Liver Neoplasms (blood, pathology)
• Lung Neoplasms (prevention & control, secondary)
• Mice
• Mice, Inbred BALB C
• Neoplasm Recurrence, Local (prevention & control)
• Neoplasm Transplantation
• Oligoribonucleotides, Antisense (administration & dosage, pharmacology)
• Phosphorothioate Oligonucleotides
• Telomerase (genetics)
• alpha-Fetoproteins (metabolism)