Oestradiol and tamoxifen inhibit murine Colon 38 cancer growth and increase the cytotoxic effect of fluorouracil.
The poor efficacy of reference chemotherapy (fluorouracil -FU) in colon cancer has resulted in a constant search for agents which could augment the action of FU. Epidemiological data, such as the decreased risk of colorectal cancer among menopausal women receiving hormonal replacement therapy, indicate the role of oestrogen in the pathogenesis of this disease. The differences between normal and neoplastic colon cells in the expression of oestrogen receptor beta (ERbeta) could confirm this association. However, the direct influence of oestrogen or tamoxifen (SERM, selective oestrogen receptor modulator) on colon cancer growth has rarely been studied. The aim of the present study was to examine the direct effects of various concentrations of oestradiol and tamoxifen (10(-4) to 10(-12) M), applied alone or together with FU, on the growth of murine Colon 38 cancer in vitro as assessed by three colorimetric methods: Mosmann's method, incorporation of BrdU into cell nuclei and the TUNEL method. At high concentrations oestradiol and tamoxifen decreased the cancer growth in a dose- and time-dependent manner (the Mosmann and BrdU methods) and at some concentrations augmented the cytotoxic action of FU (Mosmann's method). Tamoxifen exerted a very early and potent inhibitory effect, inducing even total cancer growth inhibition at the concentration of 10(-4) M (the Mosmann and BrdU methods). All the substances studied at different concentrations and at different incubation time points increased the apoptosis of tumour cells (the TUNEL method). The results indicate that oestradiol and tamoxifen inhibit Colon 38 cancer growth and increase the cytotoxic effect of FU, which confirms the role of sex steroids in colon carcinogenesis and even suggests new therapeutic schemes.
Department of Immunoendocrinology, Chair of Endocrinology, Medical University, Łódź. emotylek@poczta.onet.pl
Ewelina
E
Motylewska
Hanna
H
Lawnicka
Gabriela
G
Mełeń-Mucha
D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D003110:Colonic Neoplasms / Q000188:drug therapy*; D004305:Dose-Response Relationship, Drug; D004958:Estradiol / Q000494:pharmacology*; D005472:Fluorouracil / Q000494:pharmacology*; D066298:In Vitro Techniques; D051189:Murinae; D013629:Tamoxifen / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D013629:Tamoxifen; D004958:Estradiol; D005472:Fluorouracil