Antrodia cinnamomea alleviates cisplatin-induced hepatotoxicity and enhances chemo-sensitivity of line-1 lung carcinoma xenografted in BALB/cByJ mice.
Antrodia cinnamomea alleviates cisplatin-induced hepatotoxicity and enhances chemo-sensitivity of line-1 lung carcinoma xenografted in BALB/cByJ mice.
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DOI：
10.18632/oncotarget.4348
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发表时间：
2015-09-22
期刊：
影响因子：
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通讯作者：
Wu CJ
中科院分区：
文献类型：
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作者：
Huang TH;Chiu YH;Chan YL;Wang H;Li TL;Liu CY;Yang CT;Lee TY;You JS;Hsu KH;Wu CJ
虽然顺铂(顺铂II)是治疗实体肿瘤的一线药物，但它往往会产生严重的副作用。治疗效果与顺铂相当甚至更好，但副作用比顺铂免费或更少的新药在癌症治疗中受到高度期待。最近的研究表明，肉桂皮(AC)除了抗癌外，还具有保肝作用。在这项研究中，我们想知道AC是否增强了顺铂的化疗敏感性和/或减轻了顺铂引起的肝毒性，以及其潜在的机制。我们的结果表明，AC在体外抑制了LINE-1肺癌细胞的增殖，并使HepG2细胞免于顺铂诱导的细胞死亡。事实上，AC和顺铂在BALB/cByJ小鼠体内协同抑制LINE-1肺癌细胞的生长。实时定量聚合酶链式反应进一步显示，AC促进了肿瘤组织中凋亡相关基因的表达，而降低了肿瘤组织中NF-κB和VEGFB的表达。在肝脏方面，AC除了减轻体重恢复外，还能减少顺铂引起的肝功能障碍、肝脏炎症和肝细胞凋亡。综上所述，AC能够通过触发肺癌细胞中凋亡相关基因的表达来提高顺铂的疗效，并通过避免顺铂诱导的肝脏炎症和细胞死亡来保护肝脏免受组织损伤。
Whereas cisplatin (cis-diamminedichloroplatinum II) is a first-line medicine to treat solid cancerous tumors, it often causes serious side effects. New medicines that have an equivalent or even better therapeutic effect but with free or less side effects than cisplatin are highly anticipated in cancer therapy. Recent reports revealed that Antrodia cinnamomea (AC) possesses hepatoprotective activity in addition to anticancer. In this study, we wanted to know whether AC enhances chemo-sensitivity of cisplatin and/or alleviates cisplatin-induced hepatotoxicity, as well as the underlying mechanisms thereof. Our results indicated that AC inhibited proliferation of line-1 lung carcinoma cells and rescued hepatic HepG2 cells from cisplatin-induced cell death in vitro. The fact is that AC and cisplatin synergized to constrain growth of line-1 lung carcinoma cells in BALB/cByJ mice. Quantitative real-time PCR further revealed that AC promoted expression of apoptosis-related genes, while it decreased expression of NF-κB and VEGF in tumor tissues. In liver, AC reduced cisplatin-induced liver dysfunctions, liver inflammation and hepatic apoptosis in addition to body weight restoration. In summary, AC is able to increase cisplatin efficacy by triggering expression of apoptosis-related genes in line-1 lung cancer cells as well as to protect liver from tissue damage by avoiding cisplatin-induced hepatic inflammation and cell death.