人类结直肠癌和小鼠模型结直肠肿瘤的性别二态性。
Sexual dimorphism of colorectal cancer in humans and colorectal tumors in a murine model.
发表日期:2024
作者:
Yair Rodríguez-Santiago, Luis Ignacio Terrazas-Valdés, Karen Elizabeth Nava-Castro, Víctor Hugo Del Río-Araiza, Claudia Angélica Garay-Canales, Jorge Morales-Montor
来源:
Disease Models & Mechanisms
摘要:
在结直肠癌中,男性的发病率高于女性,并且患有这种疾病的患者血清中性类固醇水平存在紊乱。一致地,在动物中,在不同的模型中,雄性的肿瘤生长速度比雌性更大。然而,性类固醇的作用尚未明确。为此,我们分析了主要性腺类固醇对两性的影响。我们根据从 GLOBOCAN 数据库获得的数据,将性别确定为结直肠癌的统计危险因素。为了诱导结直肠肿瘤,我们使用了氧化偶氮甲烷和硫酸葡聚糖钠的金标准化学方法。为了评估性类固醇的作用,我们对独立的雄性和雌性动物进行了性腺切除,重建并用 17β 雌二醇和二氢睾酮替代它们。最后,我们在体外测定了暴露于 17β 雌二醇、睾酮或二氢睾酮的人类细胞系的增殖情况。性别作为结直肠癌的危险因素,50岁以上的男性对结直肠癌的易感性具有统计学意义。在体内,男性比女性产生更多的肿瘤,且体积更大。在男性中,睾丸切除术可以防止肿瘤生长,而在女性中,卵巢切除术会促进肿瘤的发展。 DHT 在两性中都充当促肿瘤剂。 17β雌二醇可减少女性的肿瘤生长,但会增强男性的肿瘤生长,表现出二态性效应。体外研究表明,雌二醇可降低 HCT-116 结肠癌细胞系的增殖,而睾酮可促进这些细胞的增殖。有趣的是,二氢睾酮不会影响增殖。版权所有 © 2024 Rodríguez-Santiago、Terrazas-Valdés、Nava-Castro、Del Río-Araiza、Garay-Canales 和 Morales-Montor。
In colorectal cancer, men exhibit a higher incidence than women, and there is a disturbance in the levels of sex steroids in serum in patients with this disease. Consistently, in animals, males have greater tumor growth than females in diverse models. Nevertheless, the role of sex steroids is not well established. For that, we analyzed the effect of the principal gonadal sex steroids in both sexes. We determined sex as a statistically risk factor for colorectal cancer with data obtained from GLOBOCAN database.To induce colorectal tumors, we used the gold standard chemical method of azoxymethane and dextran sulphate of sodium. To evaluate the role of sex steroids, we gonadectomized independent males and female animals, reconstituting and substituting them with 17β estradiol and dihydrotestosterone. Finally, we determined, in vitro, the proliferation of a human cell line exposed to 17β estradiol, testosterone, or dihydrotestosterone. Sex, as a risk factor for colorectal cancer, showed a statistically significant susceptibility of men over 50 years old.In vivo, males develop a greater number of tumors and with a larger size than females. In males, orchiectomy prevents tumor growth, whereas in females, ovariectomy promotes the development of neoplasms. DHT acts as a protumoral agent in both sexes. 17β estradiol reduces tumor growth in females but enhances it in males, showing a dimorphic effect. In vitro studies reveal that estradiol decreases the proliferation of the HCT-116 colon cancer cell line, while testosterone boosts proliferation in these cells. Interestingly, dihydrotestosterone does not influence proliferation.Copyright © 2024 Rodríguez-Santiago, Terrazas-Valdés, Nava-Castro, Del Río-Araiza, Garay-Canales and Morales-Montor.