Brassicasterol inhibits hepatitis B virus-associated hepatocellular carcinoma development via suppression of AKT signaling pathway.
Brassicasterol inhibits hepatitis B virus-associated hepatocellular carcinoma development via suppression of AKT signaling pathway.
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DOI：
10.1186/s13027-023-00502-1
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发表时间：
2023-04-20
影响因子：
3.7
通讯作者：
Lian, Jianping
中科院分区：
文献类型：
--
作者：
Zeng, Jindi;Wu, Jiancheng;Pang, Shuijiao;Wang, Feifei;Yu, Xin;Zhang, Shouhua;Zeng, Junquan;Yan, Jinlong;Lian, Jianping
B型肝炎病毒（HBV）相关的肝细胞癌（HCC）对目前的治疗方案（如索拉非尼B）反应不佳，迫切需要开发HBV + HCC的治疗策略。阿米卡甾醇先前已显示出抗癌和抗病毒活性，然而，其对HBV + HCC的价值仍有待探索。在HBV + HCC细胞系和异种移植小鼠模型上评估油菜甾醇和索拉非尼的抑制作用。用乳酸脱氢酶法测定菜籽甾醇对正常肝细胞的细胞毒性。AKT激动剂用于鉴定油菜甾醇的靶向信号通路。阿米卡甾醇以剂量依赖性和时间依赖性方式诱导HBV + HCC细胞死亡，并且这种抑制作用比索拉非尼更有效。对正常肝细胞无明显细胞毒性。异种移植小鼠模型进一步证实了油菜甾醇对HBV + HCC生长的抑制作用。此外，信号通路分析显示，油菜甾醇处理的HBV + HCC细胞的磷酸化AKT表达水平降低，而AKT激动剂的加入可以抵消油菜甾醇对HCC的抑制作用，表明油菜甾醇抑制AKT通路在HBV + HCC细胞中表现出抗癌活性。此外，油菜甾醇对HBV−和HBV + HCC细胞的抑制水平相似。异胆甾醇通过下调AKT通路对HCC具有抗癌活性，并且这种活性不依赖于HBV感染。在线版本包含补充材料，可通过10.1186/s13027-023-00502-1获得。
Hepatitis B virus (HBV)-associated hepatocellular carcinoma (HCC) does not respond well to current treatment options like sorafenib, and there is an urgent need for developing therapeutical strategies for HBV + HCC. Brassicasterol has previously shown anti-cancer and anti-viral activities, however, its value against HBV + HCC remains to be explored. The inhibitory effect of brassicasterol and sorafenib was evaluated on HBV + HCC cell lines and xenograft mouse model. The cytotoxicity of brassicasterol on normal liver cells were measured by LDH assay. AKT agonist was used to identify the targeted signaling pathway by brassicasterol. Brassicasterol induced HBV + HCC cell death in a both dose-dependent and time-dependent manner, and such inhibition was more potent than sorafenib. Brassicasterol did not show apparent cytotoxicity to normal liver cells. Xenograft mouse model further confirmed the inhibitory effect of brassicasterol on the growth of HBV + HCC. Furthermore, signaling pathway analysis showed that brassicasterol-treated HBV + HCC cells had decreased level of phosphor-AKT expression while the addition of AKT agonist could counteract the inhibitory effect of brassicasterol on HCC, indicating that brassicasterol suppressed AKT pathway to exhibit anti-cancer activity in HBV + HCC cells. In addition, brassicasterol showed similar levels of inhibition on HBV− and HBV + HCC cells. Brassicasterol possesses anti-cancer activity against HCC through the downregulation of AKT pathway and such activity is independent of HBV infection. The online version contains supplementary material available at 10.1186/s13027-023-00502-1.
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影响因子：
2.9
作者：
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通讯作者：
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