Department of Pediatric Surgery, Guangxi Maternal and Child Health Hospital, Nanning, Guangxi Zhuang Autonomous Region, China.
Reproductive Center, Guangxi Maternal and Child Health Hospital, Nanning, Guangxi Zhuang Autonomous Region, China.
Biofactors. 2019 Nov;45(6):975-982. doi: 10.1002/biof.1545. Epub 2019 Jul 19.
Osteosarcoma (OS) refers to a malignant tumor with potential invasiveness and metastasis; however, the current chemotherapy of OS is lacking. Thus, the alternative drug for treating OS is urgent to explore. Calycosin (CC) is evidenced in our previous study to play the anti-OS benefits for suppressing cancer cell proliferation. Consequently, further investigation of CC-medicated anti-invasive and metastatic effects against OS is needed. In the current study, the clinical samples of OS patients were collected for biological and staining assays, such as enzyme-linked immunosorbent assay and polymerase chain reaction. Meanwhile, the cell line and tumor-bearing nude mice were employed in assessing antimetastatic effects of CC against OS through biochemical tests and immunoassays. As a result, the OS patients exhibited upregulated neoplastic expressions of matrix metalloproteinase 2 (MMP2) and proliferating cell nuclear antigen (PCNA), cellular mRNAs and proteins of inhibitor of nuclear factor kappa-B alpha (IκBα), and epithelial cell transforming sequence 2 (ECT2). In cell-line study, CC-treated human OS cells exhibited induced cell apoptosis, reduced cell proliferation, and cellular MMP2 and PCNA concentration, inhibited cell migration, lowered expressions of IκBα ECT2 mRNAs, and proteins. In tumor-bearing nude mice study, CC-treated mice resulted in the dose-dependent reductions of tumor weights and intracellular MMP2 contents. As shown in further assays, neoplastic expressions of interleukin 6 protein, IκBα, ECT2 mRNAs, and proteins were downregulated dose-dependently in CC-treated tumor-bearing mice. In conclusion, these investigative findings suggest that CC may play the potential anti-invasive benefits against OS through suppressing metastasis-associated IκBα/ECT2 molecular pathway.
骨肉瘤（OS）是一种具有潜在侵袭性和转移性的恶性肿瘤；然而，目前对 OS 的化疗效果不佳。因此，迫切需要探索治疗 OS 的替代药物。我们之前的研究表明，毛蕊异黄酮（CC）在抑制癌细胞增殖方面具有抗 OS 作用。因此，需要进一步研究 CC 对 OS 的抗侵袭和转移作用。在本研究中，收集了 OS 患者的临床样本进行生物学和染色检测，如酶联免疫吸附试验和聚合酶链反应。同时，采用细胞系和荷瘤裸鼠进行生化试验和免疫检测，评估 CC 对 OS 的抗转移作用。结果显示，OS 患者表现出基质金属蛋白酶 2（MMP2）和增殖细胞核抗原（PCNA）的肿瘤表达上调，细胞内 IκBα 和上皮细胞转化序列 2（ECT2）的 mRNAs 和蛋白质表达上调。在细胞系研究中，CC 处理的人 OS 细胞表现出诱导的细胞凋亡、降低的细胞增殖以及细胞内 MMP2 和 PCNA 浓度、抑制的细胞迁移、降低的 IκBα 和 ECT2 mRNAs 和蛋白质表达。在荷瘤裸鼠研究中，CC 处理的小鼠肿瘤重量和细胞内 MMP2 含量呈剂量依赖性降低。进一步的检测结果表明，CC 处理的荷瘤小鼠中，白细胞介素 6 蛋白、IκBα、ECT2 mRNAs 和蛋白质的肿瘤表达呈剂量依赖性下调。综上所述，这些研究结果表明，CC 通过抑制转移相关的 IκBα/ECT2 分子通路，可能发挥其抗 OS 侵袭的作用。
