Rodríguez-Santiago Yair, Terrazas-Valdés Luis Ignacio, Nava-Castro Karen Elizabeth, Del Río-Araiza Víctor Hugo, Garay-Canales Claudia Angélica, Morales-Montor Jorge
Departamento de Inmunología, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, Ciudad Universitaria, Ciudad de México, Mexico.
Posgrado en Ciencias Biológicas, Universidad Nacional Autónoma de México, Ciudad Universitaria, Ciudad de México, Mexico.
Front Oncol. 2024 Aug 6;14:1398175. doi: 10.3389/fonc.2024.1398175. eCollection 2024.
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.
在结直肠癌中，男性的发病率高于女性，且该病患者血清中的性类固醇水平存在紊乱。同样，在动物实验中，在多种模型中雄性动物的肿瘤生长都比雌性动物更显著。然而，性类固醇的作用尚未完全明确。为此，我们分析了主要性腺性类固醇在两性中的作用。我们利用从全球癌症数据库（GLOBOCAN）获得的数据，将性别确定为结直肠癌的一个统计学风险因素。
为诱导结直肠癌肿瘤，我们采用了金标准化学方法，即使用氧化偶氮甲烷和葡聚糖硫酸钠。为评估性类固醇的作用，我们对雄性和雌性动物进行去势手术，然后用17β-雌二醇和双氢睾酮进行重建和替代。最后，我们在体外测定了暴露于17β-雌二醇、睾酮或双氢睾酮的人细胞系的增殖情况。性别作为结直肠癌的一个风险因素，显示出50岁以上男性具有统计学上显著的易感性。
在体内，雄性动物比雌性动物产生更多且更大的肿瘤。在雄性动物中，睾丸切除术可阻止肿瘤生长，而在雌性动物中，卵巢切除术则促进肿瘤的发展。双氢睾酮在两性中均起促肿瘤作用。17β-雌二醇可降低雌性动物的肿瘤生长，但增强雄性动物的肿瘤生长，显示出一种双态效应。体外研究表明，雌二醇可降低HCT-116结肠癌细胞系的增殖，而睾酮则促进这些细胞的增殖。有趣的是，双氢睾酮对增殖没有影响。
