Overexpression of caveolin-1 reduces Taxol resistance in human osteosarcoma cells by attenuating PI3K-Akt-JNK dependent autophagy.
Overexpression of caveolin-1 reduces Taxol resistance in human osteosarcoma cells by attenuating PI3K-Akt-JNK dependent autophagy.
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DOI：
10.3892/etm.2016.3713
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发表时间：
2016-11
影响因子：
2.7
通讯作者：
Mo H
中科院分区：
文献类型：
--
作者：
Guan J;Yuan Z;He J;Wu Z;Liu B;Lin X;Mo L;Mo H
Caveolin-1（CAV-1）是一种癌蛋白和肿瘤抑制因子，在正常成骨细胞中高表达。虽然研究人员已经研究了它在人类骨肉瘤中的作用，但caveolin-1在骨肉瘤中的作用机制仍然未知。在本研究中，Saos-2和U-2 OS细胞用逐渐增加紫杉醇浓度的连续诱导方案培养6个月以建立耐药细胞系。通过蛋白质印迹法和定量聚合酶链反应检测骨肉瘤细胞中CAV-1的表达水平。使用短发夹RNA慢病毒载体实现CAV-1敲低，并通过MTT测定分析细胞活力。研究了小窝蛋白-1对自噬的影响，并在紫杉醇耐药的骨肉瘤细胞中鉴定了小窝蛋白-1的下调和自噬的增加。此外，本研究的结果表明，下调小窝蛋白-1促进自噬和诱导骨肉瘤细胞对紫杉醇的耐药性。值得注意的是，CAV-1的过表达通过减少自噬使耐药细胞对紫杉醇重新敏感。总之，CAV-1在泰素耐药的骨肉瘤细胞中被证明是下调的，并且CAV-1在人骨肉瘤细胞中的过表达通过减弱PI 3 K-Akt-JNK依赖的自噬来抑制泰素耐药。目前的研究结果表明，进一步调查CAV-1的作用，紫杉醇耐药是必要的。CAV-1的检测有可能作为评价骨肉瘤患者治疗和预后的指标。
Caveolin-1 (CAV-1), which is an oncoprotein and a tumor suppressor, is highly expressed in normal osteoblasts. Although researchers have investigated its role in human osteosarcoma, the mechanism of caveolin-1 action in osteosarcoma remains unknown. In the present study, Saos-2 and U-2 OS cells were cultured with a continuous induction protocol of gradually increasing Taxol concentration for 6 months to establish drug-resistant cell lines. CAV-1 expression levels in osteosarcoma cells were detected via western blotting and quantitative polymerase chain reaction. CAV-1 knockdown was achieved using a short hair-pin RNA lentivirus vector, and cell viability was analyzed by MTT assay. The effect of caveolin-1 on autophagy was investigated, and the downregulation of caveolin-1 and increased autophagy was identified in Taxol-resistant osteosarcoma cells. In addition, the results of the present study demonstrated that downregulation of caveolin-1 promotes autophagy and induces osteosarcoma cell resistance to Taxol. Notably, overexpression of CAV-1 resensitized drug-resistant cells to Taxol via declined autophagy. In conclusion, CAV-1 was demonstrated to be downregulated in Taxol-resistant osteosarcoma cells, and overexpression of CAV-1 in human osteosarcoma cells suppressed Taxol resistance by attenuating PI3K-Akt-JNK-dependent autophagy. The present findings suggest that further investigation into CAV-1's role in Taxol resistance is warranted. In the future, detection of CAV-1 may be used as an indicator to evaluate the treatment and prognosis of patients with osteosarcoma.
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影响因子：
3.7
作者：
Shiroto T;Romero N;Sugiyama T;Sartoretto JL;Kalwa H;Yan Z;Shimokawa H;Michel T
通讯作者：
Michel T
影响因子：
4.2
作者：
Wang, Li;Zhang, Huiping;Qian, Jihong
通讯作者：
Qian, Jihong
影响因子：
--
作者：
Sun NK;Huang SL;Lu HP;Chang TC;Chao CC
通讯作者：
Chao CC
影响因子：
13.3
作者：
Cicchini M;Chakrabarti R;Kongara S;Price S;Nahar R;Lozy F;Zhong H;Vazquez A;Kang Y;Karantza V
通讯作者：
Karantza V
DOI：
10.1126/science.1254721
发表时间：
2014-12-19
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Crystal AS;Shaw AT;Sequist LV;Friboulet L;Niederst MJ;Lockerman EL;Frias RL;Gainor JF;Amzallag A;Greninger P;Lee D;Kalsy A;Gomez-Caraballo M;Elamine L;Howe E;Hur W;Lifshits E;Robinson HE;Katayama R;Faber AC;Awad MM;Ramaswamy S;Mino-Kenudson M;Iafrate AJ;Benes CH;Engelman JA
通讯作者：
Engelman JA