Department of Orthopedics, 2nd Affiliated Hospital, School of Medicine, Zhejiang University, #88 Jie Fang Road, Hangzhou, 310009 Zhejiang, People's Republic of China.
Cancer Chemother Pharmacol. 2012 Feb;69(2):317-31. doi: 10.1007/s00280-011-1699-4. Epub 2011 Jun 30.
Matrine, one of the main active components of extracts from the dry roots of Sophora flavescens, has potent anti-tumor activity in various cancer cell lines. However, the activity of matrine against osteosarcoma remains unclear. In the present study, we examined the effects of matrine on human osteosarcoma cells and explored the underlying mechanism.
Four human osteosarcoma cell lines: MG-63, U-2OS, Saos-2, and MNNG/HOS were treated by matrine and subjected to MTT assay, annexin V-FITC/PI double staining, and TUNEL assay. The activation of caspases and the expression of pro-apoptotic and anti-apoptotic factors were examined by qRT-PCR and Western blot. In addition, MNNG/HOS xenograft tumors were established in female nude BALB/c mice, and matrine was intraperitoneally (i.p.) administered to evaluate the anti-cancer capacity of matrine in vivo.
We found that matrine inhibited the proliferation and induced apoptosis of the four osteosarcoma cell lines in vitro and induced the activation of caspase-3, -8, and -9 in a dose-dependent manner. Furthermore, the pro-apoptotic factors Bax and Fas/FasL were upregulated, and the anti-apoptotic Bcl-2 was downregulated. More importantly our in vivo, studies showed that administration of matrine decreased tumor growth in a dose-dependent manner. Immunohistochemistry analysis demonstrated the downregulation of Bcl-2 and upregulation of Bax and Fas/FasL in MNNG/HOS tumor tissues following matrine treatment, consistent with the in vitro results.
Our results demonstrate that matrine inhibits the proliferation and induces apoptosis of human osteosarcoma cells in vitro and in vivo. The induction of apoptosis appears to occur through the upregulation of Fas/FasL and Bax, downregulation of Bcl-2, and activation of caspase-3, -8, and -9, which then trigger major apoptotic cascades.
苦参碱是苦参干根提取物的主要活性成分之一，在多种癌细胞系中具有很强的抗肿瘤活性。然而，苦参碱对骨肉瘤的活性尚不清楚。本研究检测了苦参碱对人骨肉瘤细胞的作用，并探讨了其作用机制。
用苦参碱处理人骨肉瘤细胞系 MG-63、U-2OS、Saos-2 和 MNNG/HOS，通过 MTT 试验、Annexin V-FITC/PI 双染和 TUNEL 试验检测细胞增殖和凋亡。通过 qRT-PCR 和 Western blot 检测 caspase 激活和促凋亡及抗凋亡因子的表达。此外，建立雌性裸鼠 MNNG/HOS 异种移植瘤模型，腹腔注射苦参碱，评价苦参碱体内的抗肿瘤作用。
我们发现苦参碱在体外抑制四种骨肉瘤细胞系的增殖并诱导其凋亡，并呈剂量依赖性激活 caspase-3、-8 和 -9。此外，促凋亡因子 Bax 和 Fas/FasL 上调，抗凋亡因子 Bcl-2 下调。更重要的是，我们的体内研究表明，苦参碱呈剂量依赖性抑制肿瘤生长。免疫组化分析表明，苦参碱处理后 MNNG/HOS 肿瘤组织中 Bcl-2 下调，Bax 和 Fas/FasL 上调，与体外结果一致。
我们的研究结果表明，苦参碱在体外和体内抑制人骨肉瘤细胞的增殖并诱导其凋亡。凋亡的诱导似乎是通过 Fas/FasL 和 Bax 的上调、Bcl-2 的下调以及 caspase-3、-8 和 -9 的激活来实现的，从而引发主要的凋亡级联反应。
