School of Chinese Medicine, College of Chinese Medicine, China Medical University, Taichung 40604, Taiwan.
School of Chinese Medicine for Post-Baccalaureate, I-Shou University, Kaohsiung 840, Taiwan.
Molecules. 2021 Nov 24;26(23):7105. doi: 10.3390/molecules26237105.
Tetrandrine (TET), a bisbenzylisoquinoline (BBI) alkaloid, is isolated from the plant S. Moore and has a wide range of biological activity, including anticancer properties in vitro and in vivo. At first, we established a luciferase-expressing stable clone that was named GBM 8401/ cells. Herein, the primary results indicated that TET reduced the total cell viability and induced cell apoptosis in GBM 8401/ human glioblastoma cells. However, there is no available information showing that TET suppresses glioblastoma cells in vivo. Thus, we investigated the effects and mechanisms of TET on a GBM 8401 cell-generated tumor in vivo. After the tumor volume reached 100-120 mm in subcutaneously xenografted nude mice, all of the mice were randomly divided into three groups: Group I was treated with phosphate-buffered solution (PBS) containing 0.1% dimethyl sulfoxide, Group II with 25 mg/kg of TET, and Group III with 50 mg/kg of TET. All mice were given the oral treatment of PBS or TET by gavage for 21 days, and the body weight and tumor volumes were recorded every 5 days. After treatment, individual tumors, kidneys, livers, and spleens were isolated from each group. The results showed that TET did not affect the body weights, but it significantly decreased the tumor volumes. The TET treatment at 50 mg/kg had a two-fold decrease in tumor volumes than that at 25 mg/kg when compared to the control. TET decreased the total photon flux, and treatment with TET at 50 mg/kg had a lower total photon flux than that at 25 mg/kg, as measured by a Xenogen IVIS imaging system. Moreover, the higher TET treatment had lower tumor volumes and weights than those of the lower dose. The apoptosis-associated protein expression in the tumor section was examined by immunohistochemical analysis, and the results showed that TET treatment reduced the levels of c-FLIP, MCL-1, and XIAP but increased the signals of cleaved-caspase-3, -8, and -9. Furthermore, the hematoxylin and eosin (H & E) staining of kidney, liver, and spleen tissues showed no significant difference between the TET-treated and control groups. Overall, these observations demonstrated that TET suppressed subcutaneous tumor growth in a nude-mice model via the induction of cell apoptosis.
汉防己甲素（TET）是一种双苄基异喹啉（BBI）生物碱，从植物 S. Moore 中分离得到，具有广泛的生物学活性，包括体外和体内的抗癌特性。首先，我们建立了一个表达荧光素酶的稳定克隆，命名为 GBM 8401/细胞。在此，初步结果表明 TET 降低了 GBM 8401/人神经胶质瘤细胞的总细胞活力并诱导细胞凋亡。然而，目前尚无信息表明 TET 能抑制体内神经胶质瘤细胞。因此，我们研究了 TET 在皮下异种移植裸鼠体内 GBM 8401 细胞生成的肿瘤中的作用和机制。当皮下移植的裸鼠肿瘤体积达到 100-120mm 时，将所有小鼠随机分为三组：第 I 组用含 0.1%二甲基亚砜的磷酸盐缓冲液（PBS）处理，第 II 组用 25mg/kg 的 TET 处理，第 III 组用 50mg/kg 的 TET 处理。所有小鼠均通过灌胃接受 PBS 或 TET 治疗 21 天，每 5 天记录一次体重和肿瘤体积。治疗后，从每组中分离出单个肿瘤、肾脏、肝脏和脾脏。结果表明，TET 不影响体重，但显著降低了肿瘤体积。与对照组相比，TET 治疗 50mg/kg 时肿瘤体积减少了两倍。TET 降低了总光子通量，通过 Xenogen IVIS 成像系统测量，TET 治疗 50mg/kg 时的总光子通量低于 25mg/kg。此外，较高剂量的 TET 治疗比低剂量的 TET 治疗具有更低的肿瘤体积和重量。通过免疫组织化学分析检查肿瘤切片中的凋亡相关蛋白表达，结果表明 TET 处理降低了 c-FLIP、MCL-1 和 XIAP 的水平，但增加了 cleaved-caspase-3、-8 和 -9 的信号。此外，肾脏、肝脏和脾脏组织的苏木精和伊红（H & E）染色显示 TET 处理组与对照组之间无显著差异。总的来说，这些观察结果表明，TET 通过诱导细胞凋亡抑制裸鼠皮下肿瘤生长。
