Fangchinoline suppresses the proliferation, invasion and tumorigenesis of human osteosarcoma cells through the inhibition of PI3K and downstream signaling pathways.
Fangchinoline suppresses the proliferation, invasion and tumorigenesis of human osteosarcoma cells through the inhibition of PI3K and downstream signaling pathways.
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防己诺林通过抑制PI3K及下游信号通路抑制人骨肉瘤细胞的增殖、侵袭和致瘤
DOI：
10.3892/ijmm.2017.3013
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发表时间：
2017-08
影响因子：
5.4
通讯作者：
Qian Y
中科院分区：
文献类型：
--
作者：
Li X;Yang Z;Han W;Lu X;Jin S;Yang W;Li J;He W;Qian Y
骨肉瘤是最常见的恶性骨肿瘤。大多数被诊断为骨肉瘤的患者年龄都在20岁以下。骨肉瘤细胞增殖迅速，并侵袭其他组织。目前，新辅助化疗是预防骨肉瘤进展的主要药效学策略。然而，这一策略的不利影响限制了其长期应用。以往的研究表明，防己碱对多种肿瘤细胞具有抗肿瘤作用，但其对骨肉瘤细胞的作用尚不清楚。本研究评价了防己碱在体外对骨肉瘤细胞增殖、凋亡、迁移、侵袭和体内成瘤的影响，并探讨了其可能的作用机制。防己甲素作用于MG63和U20S细胞后，细胞增殖明显降低，细胞凋亡率显著增加。防己甲素能明显抑制MG63细胞的迁移和侵袭。防己内酯处理的MG63细胞中，磷脂酰肌醇3-激酶(PI3K)和Aktp-Thr308的表达显著降低。此外，防己甲素处理的MG63细胞中PI3K下游的细胞周期蛋白D1和基质金属蛋白酶2和9的表达下调，caspase-3和caspase-8的表达上调。此外，防己碱能抑制皮下注射骨肉瘤细胞的Balb/c小鼠的骨肉瘤生长。提示防己碱可能通过抑制骨肉瘤细胞的增殖、迁移和侵袭，以及促进骨肉瘤细胞的凋亡来抑制骨肉瘤的进展。此外，我们的结果提示，防己甲素抗肿瘤作用的机制可能与抑制PI3K及其下游信号通路有关。
Osteosarcoma is the most common malignant bone tumor. Most patients diagnosed with osteosarcoma are less than 20 years of age. Osteosarcoma cells proliferate rapidly and invade other tissues. At present, neoadjuvant chemotherapy is the primary pharmacodynamic strategy to prevent the progression of osteosarcoma. However, adverse effects of this strategy limit its long-term application. Previous research has shown that fangchinoline exerts antitumor effects on several types of tumor cells; however, its effect on osteosarcoma cells remains unknown. The present study evaluated the effects of fangchinoline on the proliferation, apoptosis, migration and invasion of osteosarcoma cells in vitro and on their tumorigenesis in vivo and determined the possible underlying mechanism of action. Fangchinoline-treated MG63 and U20S cells showed significantly decreased proliferation and significantly increased apoptosis. Fangchinoline markedly suppressed the migration and invasion of the MG63 cells. Fangchinoline-treated MG63 cells showed significantly decreased expression of phosphoinositide 3-kinase (PI3K) and Aktp-Thr308. Moreover, fangchinoline-treated MG63 cells showed downregulated expression of cyclin D1 and matrix metalloproteinase 2 and 9, which act downstream of PI3K, and upregulated expression of caspase-3 and caspase-8. Furthermore, fangchinoline suppressed the growth of subcutaneous osteosarcoma tumors in Balb/c mice subcutaneously injected with osteosarcoma cells. These findings suggest that fangchinoline inhibits the progression of osteosarcoma by suppressing the proliferation, migration and invasion and by accelerating the apoptosis of osteosarcoma cells. In addition, our results suggest that the mechanism underlying the antitumor effects of fangchinoline involve the inhibition of PI3K and its downstream signaling pathways.
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影响因子：
4.8
作者：
Keenan, SM;Lents, NH;Baldassare, JJ
通讯作者：
Baldassare, JJ
DOI：
10.3109/14756360902932792
发表时间：
2010-02-01
影响因子：
5.6
作者：
Gulcin, Ilhami;Elias, Riad;Topal, Fevzi
通讯作者：
Topal, Fevzi
影响因子：
7.3
作者：
Wang, Ning;Pan, Weidong;Feng, Yibin
通讯作者：
Feng, Yibin
影响因子：
--
作者：
Jones KB
通讯作者：
Jones KB
影响因子：
3.7
作者：
Picci P
通讯作者：
Picci P