Xu Guangxu, Zhao Ziyi, Wysham Weiya Z, Roque Dario R, Fang Ziwei, Sun Wenchuan, Yin Yajie, Deng Boer, Shen Xiaochang, Zhou Chunxiao, Bae-Jump Victoria
Department of Gynecology, Fengxian Hospital, Southern Medical University, Shanghai, China.
Division of Gynecologic Oncology, University of North Carolina at Chapel Hill, Chapel Hill, NC, United States.
Front Oncol. 2023 Aug 4;13:1219923. doi: 10.3389/fonc.2023.1219923. eCollection 2023.
Among all cancers, endometrial cancer is most strongly associated with obesity, with more than 65% of endometrial cancers attributable to obesity and being overweight. Fatty acid synthase (FAS), a key lipogenic enzyme, is expressed in endometrial cancer tumors and is associated with a worse prognosis for this disease. Orlistat, an FAS inhibitor, is an FDA-approved weight loss medication that has demonstrated anti-tumor activity in a variety of preclinical cancer models.
In this study, the mouse model of endometroid endometrial cancer was exposed to three diet interventions, including a high fat diet (obese), a low fat diet (lean) and switch from a high fat to a low fat diet, and then exposed to orlistat or placebo.
The mice fed a high-fat diet had significantly increased body weight and tumor weight compared to mice fed a low-fat diet. Switching from a high-fat diet to a low fat diet led to a reduction in mouse weight and suppressed tumor growth, as compared to both the high fat diet and low fat diet groups. Orlistat effectively decreased body weight in obese mice and inhibited tumor growth in obese, lean, and the high fat diet switch to low fat diet mouse groups through induction of apoptosis. Orlistat also showed anti-proliferative activity in nine of 11 primary cultures of human endometrial cancer.
Our findings provide strong evidence that dietary intervention and orlistat have anti-tumor activity and supports further investigation of orlistat in combination with dietary interventions for the prevention and treatment of endometrial cancer.
在所有癌症中，子宫内膜癌与肥胖的关联最为紧密，超过65%的子宫内膜癌可归因于肥胖和超重。脂肪酸合酶（FAS）是一种关键的脂肪生成酶，在子宫内膜癌肿瘤中表达，且与该疾病的较差预后相关。奥利司他是一种FAS抑制剂，是一种经美国食品药品监督管理局（FDA）批准的减肥药物，已在多种临床前癌症模型中显示出抗肿瘤活性。
在本研究中，将子宫内膜样子宫内膜癌小鼠模型暴露于三种饮食干预中，包括高脂肪饮食（肥胖）、低脂肪饮食（瘦）以及从高脂肪饮食转换为低脂肪饮食，然后给予奥利司他或安慰剂。
与喂食低脂肪饮食的小鼠相比，喂食高脂肪饮食的小鼠体重和肿瘤重量显著增加。与高脂肪饮食组和低脂肪饮食组相比，从高脂肪饮食转换为低脂肪饮食导致小鼠体重减轻并抑制肿瘤生长。奥利司他有效降低了肥胖小鼠的体重，并通过诱导细胞凋亡抑制了肥胖、瘦以及从高脂肪饮食转换为低脂肪饮食的小鼠组中的肿瘤生长。奥利司他在11个人类子宫内膜癌原代培养物中的9个中也显示出抗增殖活性。
我们的研究结果提供了有力证据，表明饮食干预和奥利司他具有抗肿瘤活性，并支持进一步研究奥利司他与饮食干预联合用于子宫内膜癌的预防和治疗。
