Zhang Wenkan, Lei Zhong, Meng Jiahong, Li Guoqi, Zhang Yuxiang, He Jiaming, Yan Weiqi
Department of Orthopedics Research Institute, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310009, People's Republic of China.
Department of Orthopedic Surgery, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310009, People's Republic of China.
Onco Targets Ther. 2019 Dec 31;12:11651-11665. doi: 10.2147/OTT.S226850. eCollection 2019.
Osteosarcoma (OS) is a malignant bone tumor with easy metastasis and poor prognosis. (), a traditional Chinese medicine, was reported playing a critical role in suppressing multiple tumor progress. So we wanted to investigate the effects and molecular mechanisms of water extract of sporoderm-broken spores of (BSGLWE) on osteosarcoma.
In vitro, the effects on cell proliferation of BSGLWE in osteosarcoma cells were detected by CCK-8, colony formation assay and flow cytometry; migration ability of osteosarcoma cells was evaluated by cell scratch and transwell assays. Cell apoptosis and autophagy were tested by transmission electron microscopy (TEM). Potential signaling pathways were detected by Western blotting and immunofluorescence. In xenograft orthotopic model, the luminescence intensity measured by an in vivo bioluminescence imaging system, and the expression of related proteins in tumor cells were assessed by IHC analysis.
BSGLWE suppressed the proliferation and migration of osteosarcoma cells in a dose-dependent manner, and osteosarcoma cell cycle progression at the G2/M phase was arrested by the BSGLWE. In addition, increased apoptosis-related protein expression meant BSFLWE induced caspase-dependent apoptosis of osteosarcoma cells. TEM results indicated that BSGLWE promoted the formation of apoptotic bodies and autophagosomes in HOS and U2 cells. Western blotting or immunofluorescence and rescue assay revealed that BSGLWE blocked autophagic flux by inducing initiation of autophagy and increasing autophagosome accumulation of osteosarcoma cells. BSGLWE not only repressed the angiogenesis in the mouse model, but also induced apoptosis and blocked autophagy in vivo.
BSGLWE inhibits osteosarcoma progression.
骨肉瘤（OS）是一种恶性骨肿瘤，易发生转移且预后较差。据报道，中药（此处原文缺失具体中药名称）在抑制多种肿瘤进展中发挥关键作用。因此，我们旨在研究破壁孢子粉水提取物（BSGLWE）对骨肉瘤的作用及其分子机制。
在体外，通过CCK-8法、集落形成试验和流式细胞术检测BSGLWE对骨肉瘤细胞增殖的影响；通过细胞划痕试验和Transwell试验评估骨肉瘤细胞的迁移能力。通过透射电子显微镜（TEM）检测细胞凋亡和自噬。通过蛋白质免疫印迹法和免疫荧光法检测潜在的信号通路。在异种移植原位模型中，通过体内生物发光成像系统测量发光强度，并通过免疫组化分析评估肿瘤细胞中相关蛋白的表达。
BSGLWE以剂量依赖性方式抑制骨肉瘤细胞的增殖和迁移，并且BSGLWE使骨肉瘤细胞周期在G2/M期的进程停滞。此外，凋亡相关蛋白表达增加意味着BSFLWE诱导骨肉瘤细胞发生caspase依赖性凋亡。TEM结果表明，BSGLWE促进了HOS和U2细胞中凋亡小体和自噬体的形成。蛋白质免疫印迹法、免疫荧光法及拯救试验表明，BSGLWE通过诱导自噬起始并增加骨肉瘤细胞自噬体积累来阻断自噬流。BSGLWE不仅在小鼠模型中抑制血管生成，还在体内诱导凋亡并阻断自噬。
BSGLWE抑制骨肉瘤进展。
