槐耳颗粒逆转肝癌细胞对索拉非尼耐药的初步研究
Preliminary Study on Reversal of Sorafenib Resistance of Hepatocellular Carcinoma Cells by Huaier Granule
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摘要: 目的 初步探讨槐耳颗粒对索拉非尼(Sorafenib)耐药肝癌细胞BEL-7402/S的作用及其相关机制。方法 CCK-8法测定槐耳颗粒对BEL-7402/S细胞的增殖-毒性作用以及对Sorafenib的耐药逆转倍数;qPCR及Western blot法检测槐耳颗粒对BEL-7402/S细胞的缺氧诱导因子-1α(HIF-1α)及血管内皮生长因子(VEGF) mRNA和蛋白表达水平的影响。结果 槐耳颗粒能够抑制BEL-7402/S细胞的活性;在无显著细胞毒性的剂量下,槐耳颗粒能够部分逆转BEL-7402/S细胞对Sorafenib的耐药,其耐药逆转倍数为2.08;qPCR结果显示槐耳颗粒可以下调BEL-7402/S细胞中HIF-1α的mRNA水平,但对VEGF的mRNA水平无显著性影响;Western blot结果显示槐耳颗粒可以降低HIF-1α、VEGF的蛋白表达水平。结论 槐耳颗粒可能具有部分逆转BEL-7402/S细胞对Sorafenib耐药的作用,其机制可能与降低HIF-1α以及VEGF的表达水平有关。Abstract: OBJECTIVE To investigate the effect and related mechanism of Huaier granule on Sorafenib-resistant hepatocellular carcinoma cells BEL-7402/S. METHODS The proliferation-toxicity effect of Huaier granule on BEL-7402/S cells and the reversal multiple of drug resistance to Sorafenib were measured by CCK-8 assays. The effects of Huaier granule on the mRNA and protein levels of hypoxia inducible factor-1α (HIF-1α) and vascular endothelial growth factor (VEGF) in BEL-7402/S cells were detected by qPCR and Western blot, respectively. RESULTS Huaier granule inhibited the activities of BEL-7402/S cells, and partially reversed the resistance of BEL-7402/S cells to Sorafenib at the dose of no significant cytotoxicity, and the reversal multiple of drug resistance was 2.08; the results of qPCR showed that Huaier granule may down-regulate the mRNA level of HIF-1α in BEL-7402/S cells, but had no significant effect on the mRNA level of VEGF. The results of Western blot showed that Huaier granule may down-regulate the protein levels of HIF-1α and VEGF in BEL-7402/S cells. CONCLUSION Huaier granule may partially reverse the drug resistance of BEL-7402/S cells to Sorafenib, and its mechanism may be related to the decrease of the expression of HIF-1α and VEGF.
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Key words:
- Huaier granule /
- Sorafenib /
- hepatocellular carcinoma /
- drug resistance
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