Effects of seocalcitol, TTNPB, phytol or their combinations on MNU-induced carcinogenesis of mammary gland and nuclear receptors expression in mammary tumours of female Sprague-Dawley rats
Slavomira Ondkova1, Julius Brtko1, Jan Liska1,2, Lucia Jakubikova1,3 & Dana Macejova1
1-methyl-1-nitrosourea (MNU) is a well characterized carcinogen that induces adenocarcinomas in rat mammary gland with high specifity. This model has proven to be of resemblance to human breast cancer. Synthetic analogs of vitamin D3 and retinoids have shown some promise as chemopreventive agents against chemically induced mammary gland carcinogenesis in rodents.
Female Sprague-Dawley rats were given 50 mg/kg MNU i.p. on 46th and 52nd day of age and were treated with Seocalcitol (the derivate of vitamin D3, 7 μg/kg per week), TTNPB (the RAR-selective retinoid, 0.7 μg/kg thrice per week), Phytol (500 mg/kg thrice per week) or their combinations after the first tumour was observed in animal (approx. 100th day of age) until the end of experiment.
The results have shown that combination of TTNPB and Phytol markedly reduced the number, volume and burden of tumours when compared to animals treated with TTNPB alone. Also treatment of rats with the combination of Seocalcitol and Phytol decreased number of tumours in comparison with the groups of rats (TTNPB alone or Phytol alone). Furthermore, treatment with combination of TTNPB and Phytol inhibited tumour progression. MicroPET data showed the changes of size and number of tumours during the experiment. RT-PCR method has shown that application of Seocalcitol, TTNPB, Phytol or their combinations changed expression of VDR, RAR and RXR subtypes and other nuclear receptors in mammary gland tumours. This observation was also supported by using EMSA analyses. The VEGA grant 2/0022/08.