Apc-driven colon carcinogenesis in pirc rat is strongly reduced by polyethylene glycol

作者:Femia Angelo Pietro; Becherucci Caterina; Crucitta Stefania; Caderni Giovanna
来源:International Journal of Cancer, 2015, 137(9): 2270-2273.
DOI:10.1002/ijc.29581

摘要

<jats:p>Polyethylene glycol (PEG) is one of the most powerful agents in reducing chemically induced carcinogenesis in rat colon. However, contrasting results in Min mice dampened the enthusiasm on this potentially strong and virtually safe, cancer chemopreventing agent. Pirc (F344/NTac‐Apc <jats:sup>am1137</jats:sup>) rats carrying a germline heterozygous mutation in the <jats:italic>Apc</jats:italic> gene, spontaneously develop multiple tumours in the colon thus modelling both familial adenomatous polyposis (FAP) and sporadic colorectal cancer (CRC). Given this similarity, we thought that these rats could be appropriate to test the efficacy of PEG 8000 in reducing carcinogenesis. Pirc male rats aged one month were treated with 5% PEG in drinking water for 2 or 6 months. Precancerous lesions were dramatically reduced after 2 months of PEG treatment (Mucin depleted foci (MDF)/colon were 99 ±17 and 12± 8 in Controls and PEG‐treated rats, respectively; <jats:italic>p</jats:italic> &lt; 0.001; mean ± SD). Similarly, colon tumors were significantly reduced after 6 months of treatment (tumors/rat were 8.1 ± 2.3 and 3.6 ± 2.2 in Controls and PEG‐treated rats, respectively; <jats:italic>p</jats:italic> &lt; 0.05; mean ± SD). Colon proliferation, a parameter correlated to cancer risk, was also significantly lower in PEG‐treated rats than in Controls, while apoptosis was not significantly affected. In conclusion, PEG markedly reduces colon carcinogenesis in Pirc rats mutated in <jats:italic>Apc</jats:italic>; we thus suggest that PEG may be used as chemopreventive agent to reduce cancer risk in FAP and CRC patients.</jats:p>

  • 出版日期2015-11-1