Holzapfel Nina Pauline, Shokoohmand Ali, Wagner Ferdinand, Landgraf Marietta, Champ Simon, Holzapfel Boris Michael, Clements Judith Ann, Hutmacher Dietmar Werner, Loessner Daniela
Queensland University of Technology (QUT)60 Musk Avenue, Kelvin Grove, QLD 4059, Brisbane, Australia.
Australian Prostate Cancer Research Centre-Queensland, Translational Research Institute37 Kent Street, Woolloongabba, QLD 4102, Brisbane, Australia.
Am J Cancer Res. 2017 Jun 1;7(6):1322-1336. eCollection 2017.
Mutagens like oxidants cause lesions in the DNA of ovarian and fallopian tube epithelial cells, resulting in neoplastic transformation. Reduced exposure of surface epithelia to oxidative stress may prevent the onset or reduce the growth of ovarian cancer. Lycopene is well-known for its excellent antioxidant properties. In this study, the potential of lycopene in the prevention and treatment of ovarian cancer was investigated using an intraperitoneal animal model. Lycopene prevention significantly reduced the metastatic load of ovarian cancer-bearing mice, whereas treatment of already established ovarian tumors with lycopene significantly diminished the tumor burden. Lycopene treatment synergistically enhanced anti-tumorigenic effects of paclitaxel and carboplatin. Immunostaining of tumor and metastatic tissues for Ki67 revealed that lycopene reduced the number of proliferating cancer cells. Lycopene decreased the expression of the ovarian cancer biomarker, CA125. The anti-metastatic and anti-proliferative effects were accompanied by down-regulated expression of and EMT markers, decreased protein expression of integrin α5 and reduced activation of MAPK. These findings indicate that lycopene interferes with mechanisms involved in the development and progression of ovarian cancer and that its preventive and therapeutic use, combined with chemotherapeutics, reduces the tumor and metastatic burden of ovarian cancer .
像氧化剂这样的诱变剂会导致卵巢和输卵管上皮细胞的DNA损伤,从而引发肿瘤转化。减少表面上皮细胞暴露于氧化应激下可能会预防卵巢癌的发生或减缓其生长。番茄红素以其出色的抗氧化特性而闻名。在本研究中,使用腹腔内动物模型研究了番茄红素在预防和治疗卵巢癌方面的潜力。番茄红素预防显著降低了荷卵巢癌小鼠的转移负荷,而用番茄红素治疗已形成的卵巢肿瘤则显著减轻了肿瘤负担。番茄红素治疗协同增强了紫杉醇和卡铂的抗肿瘤作用。对肿瘤和转移组织进行Ki67免疫染色显示,番茄红素减少了增殖癌细胞的数量。番茄红素降低了卵巢癌生物标志物CA125的表达。抗转移和抗增殖作用伴随着E-钙黏蛋白和上皮-间质转化(EMT)标志物表达下调、整合素α5蛋白表达降低以及丝裂原活化蛋白激酶(MAPK)激活减少。这些发现表明,番茄红素干扰了卵巢癌发生和发展过程中的相关机制,并且其预防和治疗用途与化疗药物联合使用可减轻卵巢癌的肿瘤和转移负担。