Department of Spinal Surgery, Beijing Shijitan Hospital, Capital Medical University, Beijing 100038, P.R. China.
Mol Med Rep. 2018 Jan;17(1):1022-1030. doi: 10.3892/mmr.2017.7965. Epub 2017 Nov 6.
Osteosarcoma remains the most prevalent primary malignant bone tumor in children and young adults globally. Therefore, novel and highly effective antitumor agents are urgently required. Elemene is a natural plant compound extracted from the medicinal Chinese herb, Rhizomazedoariae, which has been employed as an antitumor agent for the treatment of a number of tumors, including osteosarcoma. However, the mechanisms underlying its antitumor effect are currently unclear. The human osteosarcoma cell lines, MG‑63 and U2OS, were employed in the present study. MTT, migration, transwell invasion and terminal deoxynucleotidyltransferase‑mediated deoxy‑UTP‑fluorescein nick end‑labeling assays were performed to evaluate cell viability, migration, invasion and apoptosis, respectively. Western blotting and immunohistochemistry analyses were performed to measure the levels of renin‑angiotensin system (RAS) components. In order to evaluate the effect of elemene on tumor weight and volume, MG‑63 and U2OS cells were injected into mice. Treatment of osteosarcoma cell lines, MG‑63 and U2OS, with elemene led to the inhibition of cell viability, migration and invasion, as well as induction of cell apoptosis. In addition, elemene treatment downregulated the expression of a number of RAS components. The growth of osteosarcoma cell‑transplanted tumors in nude mice and angiotensin II expression were inhibited by elemene treatment. The results of the present study indicate that the antitumor effects of elemene may partly be due to downregulation of the RAS signaling pathway, and that RAS may be a putative pharmacological target for osteosarcoma therapy.
骨肉瘤仍然是全球儿童和青少年中最常见的原发性恶性骨肿瘤。因此，迫切需要新的、高效的抗肿瘤药物。榄香烯是一种从中药莪术中提取的天然植物化合物，已被用作治疗多种肿瘤的抗肿瘤药物，包括骨肉瘤。然而，其抗肿瘤作用的机制尚不清楚。本研究采用人骨肉瘤细胞系 MG-63 和 U2OS。通过 MTT、迁移、Transwell 侵袭和末端脱氧核苷酸转移酶介导的脱氧尿嘧啶三磷酸荧光素末端标记测定分别评估细胞活力、迁移、侵袭和细胞凋亡。通过 Western blot 和免疫组织化学分析来测量肾素-血管紧张素系统（RAS）成分的水平。为了评估榄香烯对肿瘤重量和体积的影响，将 MG-63 和 U2OS 细胞注入小鼠体内。榄香烯处理骨肉瘤细胞系 MG-63 和 U2OS 导致细胞活力、迁移和侵袭的抑制以及细胞凋亡的诱导。此外，榄香烯处理下调了许多 RAS 成分的表达。榄香烯处理抑制了裸鼠骨肉瘤细胞移植瘤的生长和血管紧张素 II 的表达。本研究的结果表明，榄香烯的抗肿瘤作用可能部分归因于 RAS 信号通路的下调，并且 RAS 可能是骨肉瘤治疗的潜在药理学靶点。
