Sclareol inhibits cell proliferation and sensitizes cells to the antiproliferative effect of bortezomib via upregulating the tumor suppressor caveolin-1 in cervical cancer cells.
Sclareol inhibits cell proliferation and sensitizes cells to the antiproliferative effect of bortezomib via upregulating the tumor suppressor caveolin-1 in cervical cancer cells.
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DOI：
10.3892/mmr.2017.6480
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发表时间：
2017-06
影响因子：
3.4
通讯作者：
Cai P
中科院分区：
文献类型：
--
作者：
Zhang T;Wang T;Cai P
香紫苏醇的抗肿瘤作用早有报道，但其抗宫颈癌的确切机制尚不清楚。本研究采用MTT法和FITC-Annexin V法检测细胞增殖和凋亡。Western blotting法检测Caveolin-1（Cav-1）和铜锌超氧化物歧化酶（SOD）1的蛋白水平，免疫共沉淀法检测Cav-1与HSC 70的相互作用。本研究发现香紫苏醇抑制HeLa细胞增殖并诱导细胞凋亡。两种癌症相关蛋白Cav 1和SOD 1被鉴定为香紫苏醇在HeLa细胞中的潜在靶点。香紫苏醇处理后，Cav 1的表达增加，SOD 1蛋白水平与Cav 1蛋白水平呈负相关。Cav 1的过表达增强了HeLa细胞对香紫苏醇处理的敏感性，并下调了SOD 1的蛋白水平，这表明Cav 1和SOD 1之间存在潜在的关联。此外，香紫苏醇通过靶向Cav 1和SOD 1，使几种癌细胞对硼替佐米的抗癌作用显着敏感。综上所述，本研究的结果表明香紫苏醇通过上调Cav 1抑制肿瘤细胞生长，并为人类癌症提供了潜在的治疗靶点。
The anticancer effect of sclareol has long been reported, however, the exact mechanisms underlying the antitumorigenic effect of sclareol in cervical carcinoma remain to be fully elucidated. The present study analyzed cell proliferation and cell apoptosis by MTT and FITC-Annexin V assays. The protein levels of caveolin-1 (Cav-1) and copper-zinc superoxide dismutase (SOD)1 were determined by western blotting, and the interaction of Cav1 and HSC70 was investigated by co-immunoprecipitation experiments. The present study found that sclareol inhibited cell proliferation and induced apoptosis in HeLa cells. Two cancer-associated proteins, Cav1 and SOD1 were identified as potential targets of sclareol in HeLa cells. The expression of Cav1 increased when the cells were treated with sclareol, and the protein level of SOD1 was negatively correlated with Cav1. The overexpression of Cav1 enhanced the sensitivity of the HeLa cells to sclareol treatment and downregulated the protein level of SOD1, which exhibited potential associations between Cav1 and SOD1. In addition, sclareol significantly sensitized several cancer cells to the anticancer effect of bortezomib by targeting Cav1 and SOD1. Taken together, the results of the present study demonstrated that sclareol inhibited tumor cell growth through the upregulation of Cav1, and provides a potential therapeutic target for human cancer.