The incidence of aggressive and resistant breast cancers is growing at alarming rates, indicating a necessity to develop better treatment strategies. Recent epidemiological and preclinical studies detected low serum levels of vitamin D in cancer patients, suggesting that vitamin D may be effective in mitigating the cancer burden. However, the molecular mechanisms of vitamin D3 (cholecalciferol, vit-D3)-induced cancer cell death are not fully elucidated. The vit-D3 efficacy of cell death activation was assessed using breast carcinoma cell lines in vitro and a widely used Ehrlich ascites carcinoma (EAC) breast cancer model in vivo in Swiss albino mice. Both estrogen receptor-positive (ER+, MCF-7) and -negative (ER-, MDA-MB-231, and MDA-MB-468) cell lines absorbed about 50% of vit-D3 in vitro over 48 h of incubation. The absorbed vit-D3 retarded the breast cancer cell proliferation in a dose-dependent manner with IC50 values ranging from 0.10 to 0.35 mM. Prolonged treatment (up to 72 h) did not enhance vit-D3 anti-proliferative efficacy. Vit-D3-induced cell growth arrest was mediated by the upregulation of p53 and the downregulation of cyclin-D1 and Bcl2 expression levels. Vit-D3 retarded cell migration and inhibited blood vessel growth in vitro as well as in a chorioallantoic membrane (CAM) assay. The intraperitoneal administration of vit-D3 inhibited solid tumor growth and reduced body weight gain, as assessed in mice using a liquid tumor model. In summary, vit-D3 cytotoxic effects in breast cancer cell lines in vitro and an EAC model in vivo were associated with growth inhibition, the induction of apoptosis, cell cycle arrest, and the impediment of angiogenic processes. The generated data warrant further studies on vit-D3 anti-cancer therapeutic applications.
侵袭性和耐药性乳腺癌的发病率正以惊人速度增长，表明亟需开发更有效的治疗策略。近期流行病学及临床前研究发现癌症患者血清维生素D水平偏低，提示维生素D可能有助于减轻癌症负担。然而维生素D3（胆钙化醇）诱导癌细胞死亡的分子机制尚未完全阐明。本研究通过体外乳腺癌细胞系及体内瑞士白化小鼠广泛使用的艾氏腹水癌模型，评估了维生素D3激活细胞死亡的效能。体外培养48小时后，雌激素受体阳性（ER+，MCF-7）与阴性（ER-，MDA-MB-231及MDA-MB-468）细胞系均能吸收约50%的维生素D3。吸收的维生素D3以剂量依赖方式抑制乳腺癌细胞增殖，半数抑制浓度值介于0.10至0.35 mM之间。延长处理时间（至72小时）并未增强维生素D3的抗增殖效果。维生素D3诱导的细胞生长停滞是通过上调p53表达、下调细胞周期蛋白D1和Bcl2表达水平实现的。维生素D3在体外及绒毛尿囊膜实验中均能抑制细胞迁移和血管生成。通过小鼠液体肿瘤模型评估发现，腹腔注射维生素D3可抑制实体瘤生长并减缓体重增加。综上所述，维生素D3在体外乳腺癌细胞系及体内艾氏腹水癌模型中产生的细胞毒性效应，与生长抑制、细胞凋亡诱导、细胞周期阻滞及血管生成过程受阻相关。本研究数据为维生素D3抗癌治疗应用的深入研究提供了依据。
肿瘤(癌症)患者之家