Tamoxifen decreases ovarian toxicity without compromising cancer treatment in a rat model of mammary cancer

他莫昔芬可降低乳腺癌大鼠模型的卵巢毒性,且不会影响癌症治疗

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作者:Anna Nynca, Sylwia Swigonska, Monika Ruszkowska, Agnieszka Sadowska, Karina Orlowska, Tomasz Molcan, Kamil Myszczynski, Iwona Otrocka-Domagala, Katarzyna Paździor-Czapula, Beata Kurowicka, Brian Kelli Petroff, Renata Elzbieta Ciereszko

Background

Premenopausal women diagnosed with breast cancer often face aggressive chemotherapy resulting in infertility. Tamoxifen (TAM) is a selective estrogen receptor modulator that was previously suggested as a protective agent against chemotherapy-induced ovarian failure. In the current study, we examined mechanisms of the protective action of TAM in the ovaries of tumor-bearing rats treated with the chemotherapy drug cyclophosphamide (CPA).

Conclusions

Tamoxifen shielded the ovary from the side effects of chemotherapy without lessening the tumoricidal actions of mammary cancer treatment.

Results

TAM prevented CPA-induced loss of ovarian follicular reserves. The protective TAM effect in the rat ovary partially resulted from decreased apoptosis. In addition, transcriptomic and proteomic screening also implicated the importance of DNA repair pathways as well as cell adhesion and extracellular matrix remodeling in the protective ovarian actions of TAM. Conclusions: Tamoxifen shielded the ovary from the side effects of chemotherapy without lessening the tumoricidal actions of mammary cancer treatment.

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