Estradiol and progesterone regulate proliferation and apoptosis in colon cancer

SASSO CV; SANTIANO FE; CAMPO VERDE ARBOCCÓ F; ZYLA L; SEMINO SN; PISTONE CREYDT VIRGINIA; LOPEZ FONTANA CM; CARON RW

Endocrine Connections

bioscientifica ltd

Lugar: Bristol ; Año: 2018

Epidemiological studies describe estrogens as protectors in the development of colon cancer in postmenopausal women treated with hormone replacement therapy. On the other hand, the role of progesterone in colon cancer has been minimally studied and the results are controversial. For the above, the objective of this work was to determine the hormonal regulation exerted by natural ovarian steroids on proliferation and apoptosis in an experimental model of colon cancer in ovariectomized rats treated with 17 beta-estradiol and progesterone. Sprague Dawley rats were exposed to the carcinogen 1,2-dimethylhydrazine to induce colon tumors. Thirty days later, the rats were ovariectomized and treated with estradiol (60 µg/kg), progesterone (10 mg/kg), estradiol plus progesterone(60 µg/kg and 10 mg/kg) and vehicle. We observed that the combined treatment with estradiol and progesterone resulted in a tendency to decrease colon cancer incidence and tumor multiplicity. Furthermore, we observed a decrease in PCNA expression and a greater number of apoptotic index, higher expression of caspase 3, cleaved PARP and cleaved caspase 8 in tumors, confirming the activation of the extrinsic pathway of apoptosis by the combined treatment. In addition, we observed a higher expression of estrogen receptor beta in these tumors. We conclude that the action of both hormones, estradiol and progesterone, is necessary to reduce proliferation and increase apoptosis in colon tumors, probably through estrogen receptor beta activation.