Synergistic cytotoxic effects of a combined treatment of a Pinellia pedatisecta lipid-soluble extract and cisplatin on human cervical carcinoma in vivo.
Synergistic cytotoxic effects of a combined treatment of a Pinellia pedatisecta lipid-soluble extract and cisplatin on human cervical carcinoma in vivo.
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半夏脂溶性提取物与顺铂联合治疗人宫颈癌体内协同细胞毒作用
DOI：
10.3892/ol.2017.6091
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发表时间：
2017-06
期刊：
影响因子：
2.9
通讯作者：
Xu C
中科院分区：
文献类型：
--
作者：
Zhang M;Yu Y;Zhang H;Huang H;Cai Q;Kang Y;Li G;Xu C
众所周知，草药有许多好处，包括比传统化疗药物毒性更低，副作用更少。在中医中，半夏（Pinellia pedatisecta）的根茎一直被用来治疗癌症、未确诊的肿胀和毒性红斑。然而，它的医学益处缺乏科学证据的支持。一种新的脂溶性PE提取物已被证实可以增强顺式二氯二明铂- ii （CDDP）对人宫颈癌细胞的体外细胞毒性。本研究评估了PE和CDDP对人宫颈癌的协同细胞毒作用。PE与CDDP联合治疗对小鼠异种移植物肿瘤CaSki细胞生长具有协同细胞毒性。PE对肿瘤大小和肿瘤重量均有细胞毒作用，但PE治疗组对肿瘤重量的抑制率仅为26.3%。然而，PE和CDDP共处理小鼠时，抑制率高于CDDP单独处理小鼠（分别为50.8%和68.4%）。潜在的协同机制可能是通过抑制E6/p53信号通路，恢复p53功能，诱导下游肿瘤抑制链对细胞凋亡的影响。Western blot和免疫组化分析显示，PE和CDDP联合治疗后，ate6蛋白表达明显降低。PE + CDDP联合治疗组p53表达升高。在PE和CDDP联合治疗组中，p53依赖性凋亡相关蛋白上调，包括bcl -2相关的X蛋白和cleaved caspase -9和- 3。我们的研究结果为PE和CDDP联合治疗宫颈癌作为一种新的、药理学上安全的化疗策略提供了分子基础。
Herbal medicines are known to have numerous benefits, including lower toxicity and fewer side effects than traditional chemotherapeutic drugs. In traditional Chinese medicine, the rhizome of Pinellia pedatisecta (PE) Schott has long been used to treat cancer, undiagnosed swelling and erythema toxicum. However, its medical benefits lack support from scientific evidence. A novel lipid-soluble extract from PE has been previously verified to enhance the cytotoxicity of cis-dichlorodiammineplatinum-II (CDDP) against human cervical cancer cells in vitro. The present study evaluated the synergistic cytotoxic effects of PE and CDDP against human cervical cancer. Combination therapy of PE with CDDP exhibited synergistic cytotoxicity towards CaSki cell growth in mouse xenograft tumors. PE exhibited a cytotoxic effect on tumor size and weight, although the inhibitory ratio of tumor weight was only 26.3% in the PE-treated group. However, when mice were co-treated with PE and CDDP, the inhibitory ratio was higher than that of mice treated with CDDP alone (50.8 vs. 68.4%, respectively). The potential synergistic mechanism was likely via inhibiting the signaling E6/p53 pathway, restoring p53 function and inducing downstream tumor suppressor chain effects on apoptosis. Western blot analysis and immunohistochemistry indicated thatE6protein expression was significantly decreased upon treatment with combined PE and CDDP. The expression of p53 was increased in the combined PE and CDDP treatment group. Upregulation of p53-dependent apoptosis-associated proteins, including Bcl-2-associated X protein and cleaved caspases-9 and −3, was observed in the combined PE and CDDP treatment group. Our results present a molecular basis for the future application of the combination of PE and CDDP in the treatment of cervical cancer as a novel and pharmacologically safe chemotherapeutic strategy.