West Lindsay, Yin Yajie, Pierce Stuart R, Fang Ziwei, Fan Yali, Sun Wenchuan, Tucker Katherine, Staley Allison, Zhou Chunxiao, Bae-Jump Victoria
Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, University of North Carolina at Chapel Hill Chapel Hill, NC, USA.
Department of Gynecologic Oncology, Beijing Obstetrics and Gynecology Hospital, Capital Medical University Beijing, P. R. China.
Am J Cancer Res. 2020 Dec 1;10(12):4450-4463. eCollection 2020.
Omega-3 polyunsaturated fatty acids (PUFAs), such as those found in fish oil, are thought to have anti-tumorigenic effects and may help to treat and prevent cancer, including ovarian cancer. Thus, we aimed to evaluate the potential of docosahexaenoic acid (DHA), an omega-3 PUFA, as a therapeutic agent in ovarian cancer cell lines and a transgenic mouse model of ovarian cancer. DHA significantly inhibited cellular proliferation, induced cell cycle arrest and caused apoptosis in Hey and IGROV-1 cells. Pre-treatment with the anti-oxidant, N-acetylcysteine (NAC), reversed DHA-induced caspase 3 activity and prevented DHA-reduced cell proliferation. DHA also induced cellular reactive oxygen species (ROS) and inhibited adhesion and invasion in IGROV-1 and Hey cells. Furthermore, treatment with DHA demonstrated anti-tumorigenic and anti-invasive activity in a K18-gT ; p53; Brca1 mouse model of ovarian cancer including downregulation of Ki67 and VEGF expression. The data provide a preclinical rationale for applying DHA for dietary intervention and therapeutic adjunct in patients with ovarian cancer.
ω-3多不饱和脂肪酸(PUFA),如鱼油中所含的此类脂肪酸,被认为具有抗肿瘤作用,可能有助于治疗和预防包括卵巢癌在内的癌症。因此,我们旨在评估ω-3多不饱和脂肪酸二十二碳六烯酸(DHA)作为卵巢癌细胞系和卵巢癌转基因小鼠模型治疗药物的潜力。DHA显著抑制Hey和IGROV-1细胞的细胞增殖,诱导细胞周期停滞并导致细胞凋亡。用抗氧化剂N-乙酰半胱氨酸(NAC)预处理可逆转DHA诱导的半胱天冬酶3活性,并防止DHA降低的细胞增殖。DHA还诱导IGROV-1和Hey细胞产生细胞活性氧(ROS),并抑制其黏附和侵袭。此外,在K18-gT;p53;Brca1卵巢癌小鼠模型中,DHA治疗显示出抗肿瘤和抗侵袭活性,包括下调Ki67和VEGF表达。这些数据为将DHA应用于卵巢癌患者的饮食干预和治疗辅助提供了临床前依据。