甲苯咪唑在结肠癌中的体外和体内抗癌活性:一种有前景的药物重新定位,Naunyn |
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结肠癌是最常见的癌症之一,也是全世界死亡的主要原因之一。因此,效率更高、风险更小的新的治疗方法非常有必要。甲苯咪唑(MBZ)是一种常用于治疗蠕虫感染的药物,最近作为治疗各种癌症的合适候选药物而受到关注。本研究旨在探讨 MBZ 对结肠癌的体外和体内抗癌活性和选择性指数。用 MBZ 和阿霉素(DOX;阳性对照药物)处理 HT-29(人结直肠腺癌)和 MCF-10(非致瘤上皮)细胞系。使用甲基噻唑二苯基溴化四唑(MTT)测定法估计IC50值。我们采用膜联蛋白 V-FITC 和碘化丙啶染料进行流式细胞术。在动物研究中,CT26 细胞(小鼠结肠癌)在 Bulb/C 小鼠中皮下诱导结肠癌。每隔一天对小鼠腹膜内注射 0.05 LD50,持续 35 天。最后计算存活率、肿瘤体积和肿瘤重量。我们的结果表明,HT29 和 MCF-10 细胞系 72 小时后的 IC50 值分别为 0.29 ± 0.04 µM 和 0.80 ± 0.02 µM。与正常细胞相比,MBZ 在抑制癌细胞增殖方面比 DOX 更具选择性(2. 75 vs. 2.45)。膜联蛋白 V/PI 染色表明,48 小时后,IC50 浓度的 MBZ 处理可诱导 (78 ± 12%) HT29 癌细胞系凋亡(P ≤ 0.0001)。此外,在患有结肠癌的小鼠中,与阴性对照组(重量 12.45 ± 2.0 g)相比,MBZ 显着减少了肿瘤体积(1177 ± 1109 mm 3;P ≤ 0.001)和肿瘤重量(2.30 ± 1.97 g; P ≤ 0.0001)。 ;体积 7346 ± 1077)。此外,在动物研究中,MBZ 增加了平均生存时间 (MST) 和寿命 (ILS) 百分比(分别为 51.2 ± 37% 和 93%)。这项研究表明,甲苯咪唑强烈且选择性地抑制结肠癌细胞的增殖并诱导其凋亡。因此,它可能是一种有前景的临床研究和应用药物。
"点击查看英文标题和摘要" In vitro and in vivo anticancer activity of mebendazole in colon cancer: a promising drug repositioning
Colon cancer is one of the most common cancers and one of the main causes of death worldwide. Therefore, new treatment methods with better efficiency and fewer risks are very necessary. Mebendazole (MBZ), a drug commonly used for helminthic infections, has recently received attention as a suitable candidate for the treatment of various cancers. This study aimed to investigate, in vitro and in vivo, anticancer activity and selectivity Index of MBZ on colon cancer. HT-29 (human colorectal adenocarcinoma) and MCF-10 (non-tumorigenic epithelial) cell lines were treated with MBZ and Doxorubicin (DOX; positive control drug). IC50 values were estimated using methyl thiazole diphenyl-tetrazolium bromide (MTT) assay. We employed flow cytometry using annexin V-FITC and propidium iodide dyes. For the animal study, colon cancer was subcutaneously induced by CT26 cells (mouse colon cancer) in Bulb/C mice. The mice were treated with 0.05 of LD50, intraperitoneal, every other day for 35 days. Finally, the survival rate, tumor volume, and tumor weight were calculated. Our results demonstrated that IC50 values after 72 h for HT29 and MCF-10 cell lines were 0.29 ± 0.04 µM and 0.80 ± 0.02 µM, respectively. MBZ was more selective than DOX in inhibiting the proliferation of cancer cells compared to normal cells (2. 75 vs. 2.45). Annexin V/PI staining demonstrated that MBZ treatment at IC50 concentrations induced (78 ± 12%) apoptosis in the HT29 cancer cell line after 48 h (P ≤ 0.0001). Also, in mice bearing colon cancer, MBZ significantly reduced the tumor volume (1177 ± 1109 mm3; P ≤ 0.001) and tumor weight (2.30 ± 1.97 g; P ≤ 0.0001) compared to the negative control group (weight 12.45 ± 2.0 g; volume 7346 ± 1077). Also, MBZ increases mean survival time (MST) and increase life span (ILS) percentage in the animal study (51.2 ± 37% vs 93%, respectively). This study suggests that mebendazole strongly and selectively inhibits proliferation and induces apoptosis in colon cancer cells. It may be, accordingly, a promising drug for clinical research and application. |
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