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分段香椿叶提取物诱导人骨肉瘤细胞凋亡并抑制小鼠异种移植模型中的肿瘤生长。

The Fractionated Toona sinensis Leaf Extract Induces Apoptosis of Human Osteosarcoma Cells and Inhibits Tumor Growth in a Murine Xenograft Model.

作者信息

Chen Chung-Hwan, Li Ching-Ju, Tai I-Chun, Lin Xiao-Hui, Hsu Hseng-Kuang, Ho Mei-Ling

机构信息

1 Kaohsiung Medical University, Kaohsiung, Taiwan.

2 Kaohsiung Medical University Hospital, Kaohsiung, Taiwan.

出版信息

Integr Cancer Ther. 2017 Sep;16(3):397-405. doi: 10.1177/1534735416675951. Epub 2016 Nov 22.

Abstract

BACKGROUND

Osteosarcoma is a malignant bone tumor prevalent in adolescents with poor prognosis. Toona sinensis showed potent antiproliferation effect on lung, melatonin, ovary, colon, and liver cancers. However, the effects of the species on osteosarcoma cells are rarely investigated.

RESULTS

In this study, we found fraction 1 of Toona sinensis leaf (TSL-1) resulted in inhibition of cell viability in MG-63, Saos-2, and U2OS osteosarcoma cell lines, while it only caused a moderate suppressive effect on normal osteoblasts. In addition, TSL-1 significantly elevated lactate dehydrogenase leakage and induced apoptosis and necrosis in Saos-2 cells. TSL-1 increased mRNA expression of pro-apoptotic factor Bad. Most important, TSL-1 significantly suppressed Saos-2 xenograft tumor growth in nude mice by increasing caspase-3. The IC-50 of TSL-1 for the 3 tested osteosarcoma cells is around 1/9 of that for lung cancer cells.

CONCLUSION

We demonstrated that TSL-1, a fractionated extract from TSL, caused significant cytotoxicity to osteosarcoma cells due to apoptosis. In vivo xenograft study showed that TSL-1 suppressed the growth of osteosarcoma cells at least in part by inducing apoptosis. Our results indicate that TSL-1 has potential to be a promising anti-osteosarcoma adjuvant functional plant extract.

摘要

背景

骨肉瘤是一种在青少年中普遍存在的恶性骨肿瘤,预后较差。香椿对肺癌、黑素瘤、卵巢癌、结肠癌和肝癌显示出强大的抗增殖作用。然而,该物种对骨肉瘤细胞的影响鲜有研究。

结果

在本研究中,我们发现香椿叶提取物1(TSL-1)可抑制MG-63、Saos-2和U2OS骨肉瘤细胞系的细胞活力,而对正常成骨细胞仅有中度抑制作用。此外,TSL-1显著提高乳酸脱氢酶泄漏率,并诱导Saos-2细胞凋亡和坏死。TSL-1增加促凋亡因子Bad的mRNA表达。最重要的是,TSL-1通过增加caspase-3显著抑制裸鼠体内Saos-2异种移植瘤的生长。TSL-1对3种受试骨肉瘤细胞的IC-50约为肺癌细胞的1/9。

结论

我们证明,TSL-1这种从香椿叶中提取的分离物,因诱导凋亡而对骨肉瘤细胞具有显著的细胞毒性。体内异种移植研究表明,TSL-1至少部分通过诱导凋亡抑制骨肉瘤细胞的生长。我们的结果表明,TSL-1有潜力成为一种有前景的抗骨肉瘤辅助功能性植物提取物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7bf4/5759936/2a71078f7ea5/10.1177_1534735416675951-fig1.jpg

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