Enhanced in vivo tumour response from combination of carboplatin and low-dose c-myc antisense oligonucleotides
T L Walker1, C R Dass, M A Burton
1School of Biomedical Science, Charles Sturt University, Wagga Wagga, NSW, Australia. towalker@csu.edu
Background:
Phosphorothioate oligonucleotides ([S]ODNs) contain a modified phosphate backbone. Antisense [S]ODNs targeted to specific oncogenes have been used to varying success in vivo. Carboplatin is a commonly used chemotherapeutic and is associated with chemoresistance in some human tumours. The potential for combined antisense [S]ODNs and carboplatin chemotherapy has only recently been explored in vivo.
Materials And Methods:
This study examines the effect of c-myc antisense oligomers delivered in isolation as naked DNA and in combination with carboplatin upon the growth kinetics of an in vivo transplantable adenocarcinoma using rodents.
Results:
Tumours treated with a combination of 600 microg of 15-mer c-myc phosphorothioate antisense oligodeoxyribonucleotide and an intravenous administration of carboplatin (3 mg/kg), demonstrated a significant (p<0.05) retardation in tumour growth kinetics relative to a control. Two mismatch antisense controls did not significantly inhibit tumour growth. C-myc protein studies in tumour sections failed to show significant differences in c-myc expression in any of the treated tumours.
Conclusion:
This study demonstrates that carboplatin affects the relative abundance of c-myc and that combination treatment of carboplatin and c-myc phosphorothioate antisense oligonucleotides in vivo results in synergistic tumour retardation.
Insights
Combination therapy with carboplatin and c-myc antisense oligonucleotides significantly slows tumor growth in vivo. This synergistic effect suggests a promising new approach for cancer treatment, impacting c-myc expression.
Area of Science:
- Oncology
- Molecular Biology
- Pharmacology
Background:
- Phosphorothioate oligonucleotides ([S]ODNs) are modified DNA molecules used in antisense therapy.
- Antisense [S]ODNs targeting oncogenes show variable in vivo efficacy.
- Carboplatin is a standard chemotherapy agent, but chemoresistance is a clinical challenge.
Purpose of the Study:
- To investigate the combined efficacy of c-myc antisense oligonucleotides and carboplatin.
- To evaluate the impact on tumor growth kinetics in an in vivo model.
Main Methods:
- Utilized a rodent transplantable adenocarcinoma model.
- Administered naked c-myc antisense oligodeoxyribonucleotides and carboplatin intravenously.
- Included mismatch antisense controls for comparison.
Main Results:
- Combined treatment significantly retarded tumor growth (p<0.05) compared to controls.
- Mismatch controls did not show significant tumor growth inhibition.
- No significant changes in c-myc protein expression were observed in treated tumors.
Conclusions:
- Carboplatin influences the relative abundance of c-myc.
- Combination therapy exhibits synergistic tumor retardation in vivo.
- This approach warrants further investigation for cancer treatment strategies.
Related Concept Videos
02:50Combination Therapies and Personalized Medicine
The combination of the drug acetazolamide and sulforaphane is a good example of combination therapy to treat cancer. The cells in the interior of a large tumor often die due to the hypoxic and...
01:27Tumor Immunotherapy
02:57Targeted Cancer Therapies
There are several types of targeted therapies against specific...
02:49Cancer Therapies
However, cancer treatments can pose several challenges, as therapies used to kill cancer cells are generally also toxic to normal cells. Moreover, cancer cells mutate rapidly and can develop resistance to chemical agents or radiation therapy. Besides, all types of cancer cells may not respond to the same therapy. Some cancer cells respond to one...