Luteinizing hormone compromises the in vivo anti-tumor effect of cisplatin on human epithelial ovarian cancer cells

Platinum-based chemotherapy is the most common therapeutic regimen used to treat patients with ovarian cancer. However, the emergence of drug resistance to platinum compromises the clinical success of this treatment. Epithelial ovarian cancer is usually accompanied by an increased level of luteinizing hormone (LH). Therefore, the effect of LH on platinum resistance requires further investigation. In the current study, the effect of cisplatin and/or LH on platinum resistance was examined using the SKOV3ip1 and HeyA8 models. Following therapy, tumors were examined for proliferation (ki67) and apoptosis (cleaved caspase-3). Cisplatin alone and in combination with LH significantly inhibited tumor growth in SKOV3ip1- and HeyA8-implanted mice. Treatment with LH alone had minimal effect in the models. However, treatment with cisplatin combined with LH was less effective than treatment with cisplatin alone. Additionally, ki67 counts were significantly increased and cleaved caspase-3 counts were significantly reduced in mice treated with cisplatin combined with LH compared with mice treated with cisplatin alone. Such results indicate that LH weakens the anti-tumor effect of cisplatin in vivo and that LH may contribute to the development of drug resistance to cisplatin in ovarian cancer.