Shaanxi Key Laboratory of Degradable Biomedical Materials, School of Chemical Engineering, Northwest University, 229 North Taibai Road, Xi'an, Shaanxi 710069, China.
Food Funct. 2018 Nov 14;9(11):5513-5527. doi: 10.1039/c8fo01122b.
Breast cancer is the most frequently diagnosed cancer and has become the main cause of cancer-related death among women worldwide. Traditional chemotherapy for breast cancer has serious side effects for patients, such as the first-line drug docetaxel. Ginsenoside Rg5, a rare ginsenoside and the main ingredient extracted from fine black ginseng, has been proved to have anti-breast cancer efficacy in vitro. Here, the in vivo anti-breast cancer efficacy, side effects and potential molecular mechanisms of Rg5 were investigated on a BALB/c nude mouse model of human breast cancer. The tumor growth inhibition rate of high dose Rg5 (20 mg kg-1) was 71.4 ± 9.4%, similar to that of the positive control docetaxel (72.0 ± 9.1%). Compared to docetaxel, Rg5 showed fewer side effects in the treatment of breast cancer. Treatment with Rg5 induced apoptosis and autophagy in breast cancer tissues. Rg5 was proved to induce caspase-dependent apoptosis via the activation of the extrinsic death receptor and intrinsic mitochondrial signaling pathways. The autophagy induction was related to the formation of an autophagosome and accumulation of LC3BII, P62 and critical Atg proteins. Further studies showed that Rg5 in a dose-dependent manner induced apoptosis and autophagy through the inhibition of the PI3K/Akt signaling pathway as indicated by the reduced phosphorylation level of PI3K and Akt. Taken together, Rg5 could be a novel and promising clinical antitumor drug targeting breast cancer.
乳腺癌是最常见的癌症，已成为全球女性癌症相关死亡的主要原因。传统的乳腺癌化疗对患者有严重的副作用，如一线药物多西紫杉醇。人参皂苷 Rg5 是一种罕见的人参皂苷，也是从优质黑参中提取的主要成分，已被证明在体外具有抗乳腺癌功效。在这里，我们在人乳腺癌 BALB/c 裸鼠模型上研究了 Rg5 的体内抗乳腺癌疗效、副作用和潜在的分子机制。高剂量 Rg5（20mg/kg）的肿瘤生长抑制率为 71.4%±9.4%，与阳性对照多西紫杉醇（72.0%±9.1%）相当。与多西紫杉醇相比，Rg5 在治疗乳腺癌方面副作用较少。Rg5 处理诱导乳腺癌组织细胞凋亡和自噬。Rg5 通过激活外源性死亡受体和内源性线粒体信号通路，被证明能诱导 caspase 依赖性细胞凋亡。自噬的诱导与自噬体的形成和 LC3BII、P62 和关键 Atg 蛋白的积累有关。进一步的研究表明，Rg5 通过抑制 PI3K/Akt 信号通路，以剂量依赖的方式诱导细胞凋亡和自噬，这表现为 PI3K 和 Akt 的磷酸化水平降低。综上所述，Rg5 可能是一种针对乳腺癌的新型有前途的临床抗肿瘤药物。
