Antitumor Effects of Systemic DNAse I and Proteases in an In Vivo Model

作者:Trejo Becerril Catalina; Perez Cardenas Enrique; Gutierrez Diaz Blanca; De La Cruz Siguenza Desiree; Taja Chayeb Lucia; Gonzalez Ballesteros Mauricio; Garcia Lopez Patricia; Chanona Jose; Duenas Gonzalez Alfonso*
来源:Integrative Cancer Therapies, 2016, 15(4): NP35-NP43.
DOI:10.1177/1534735416631102

摘要

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 treatment was 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.

  • 出版日期2016-12