Related Experiment Video
Updated: Mar 21, 2026
Evaluating the Effectiveness of Cancer Drug Sensitization In Vitro and In Vivo
Published on: February 6, 2015
Antitumor Effects of Systemic DNAse I and Proteases in an In Vivo Model
Catalina Trejo-Becerril1, Enrique Pérez-Cardenas1, Blanca Gutiérrez-Díaz1
1Instituto Nacional de Cancerología, México City, Mexico.
Abstract:
Background Cell-free DNA circulates in cancer patients and induces in vivo cell transformation and cancer progression in susceptible cells. Based on this, we hypothesized that depletion of circulating DNA with DNAse I and a protease mix could have antitumor effects. Study design The study aimed to demonstrate that DNAse I and a protease mix can degrade in vitro DNA and proteins from the serum of healthy individuals and cancer patients, and in vivo in serum of Wistar rats,. Moreover, the antitumor effect of the systemically administered enzyme mix treatmentwas evaluated in nude mice subcutaneously grafted with the human colon cancer cell line SW480. Results The serum DNA of cancer patients or healthy individuals was almost completely degraded in vitro by the enzymatic treatment, but no degradation was found with the enzymes given separately. The intravenous administration of the enzymes led to significant decreases in DNA and proteins from rat serum. No antitumor effect was observed in immunodeficient mice treated with the enzymes given separately. In contrast, the animals that received both enzymes exhibited a marked growth inhibition of tumors, 40% of them having pathological complete response. Conclusion This study demonstrated that systemic treatment with DNAse I and a protease mix in rats decreases DNA and proteins from serum and that this treatment has antitumor effects. Our results support the hypothesis that circulating DNA could have a role in tumor progression, which can be offset by depleting it. Further studies are needed to prove this concept.
Insights
Depleting circulating cell-free DNA and proteins with DNAse I and protease mix showed significant antitumor effects in mice. This enzyme combination reduced tumor growth and achieved complete responses, supporting DNAse
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- Cell-free DNA (cfDNA) in cancer patients' circulation can promote tumor progression.
- Targeting circulating cfDNA is a potential strategy for cancer therapy.
Purpose of the Study:
- To investigate the in vitro and in vivo degradation of DNA and proteins by DNAse I and a protease mix.
- To evaluate the antitumor efficacy of this enzyme combination in a colon cancer mouse model.
Main Methods:
- In vitro degradation assays using serum from healthy individuals and cancer patients.
- In vivo administration of DNAse I and protease mix in Wistar rats to assess serum component reduction.
- Evaluation of tumor growth inhibition in nude mice bearing human colon cancer xenografts treated with the enzyme mix.
Main Results:
- Combined DNAse I and protease treatment effectively degraded cfDNA and proteins in vitro and in vivo.
- Systemic administration of the enzyme combination significantly inhibited colon cancer xenograft growth in mice.
- 40% of treated mice achieved pathological complete response, indicating a potent antitumor effect.
Conclusions:
- Systemic administration of DNAse I and a protease mix demonstrates significant antitumor activity.
- Depletion of circulating DNA and proteins via this enzymatic approach can counteract tumor progression.
- Further research is warranted to validate this novel therapeutic strategy.
