雷公藤红素可以增强藤黄酸对口腔鳞状细胞癌的抗癌作用。
The NF-kappa B inhibitor, celastrol, could enhance the anti-cancer effect of gambogic acid on oral squamous cell carcinoma.
机构信息
Department of Oral and Maxillofacial Surgery, College of Stomatology, Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200011, PR China.
出版信息
BMC Cancer. 2009 Sep 25;9:343. doi: 10.1186/1471-2407-9-343.
BACKGROUND
Gambogic acid (GA) is a major active ingredient of gamboge, a widely used traditional Chinese medicine that has been reported to be a potent cytotoxic agent against some malignant tumors. Many studies have shown that the NF-kappa B signaling pathway plays an important role in anti-apoptosis and the drug resistance of tumor cells during chemotherapy. In this study, the effects and mechanisms of GA and the NF-kappa B inhibitor celastrol on oral cancer cells were investigated.
METHODS
Three human oral squamous cell carcinoma cell lines, Tca8113, TSCC and NT, were treated with GA alone, celastrol alone or GA plus celastrol. Cytotoxicity was assessed by MTT assay. The rate of apoptosis was examined with annexin V/PI staining as well as transmission electronic microscopy in Tca8113 cells. The level of constitutive NF-kappa B activity in oral squamous cell carcinoma cell lines was determined by immunofluorescence assays and nuclear extracts and electrophoretic mobility shift assays (EMSAs) in vitro. To further investigate the role of NF-kappa B activity in GA and celastrol treatment in oral squamous cell carcinoma, we used the dominant negative mutant SR-IkappaBalpha to inhibit NF-kappa B activity and to observe its influence on the effect of GA.
RESULTS
The results showed that GA could inhibit the proliferation and induce the apoptosis of the oral squamous cell carcinoma cell lines and that the NF-kappa B pathway was simultaneously activated by GA treatment. The minimal cytotoxic dose of celastrol was able to effectively suppress the GA-induced NF-kappa B pathway activation. Following the combined treatment with GA and the minimal cytotoxic dose of celastrol or the dominant negative mutant SR-IkappaBalpha, proliferation was significantly inhibited, and the apoptotic rate of Tca8113 cells was significantly increased.
CONCLUSION
The combination of GA and celastrol has a synergistic antitumor effect. The effect can be primarily attributed to apoptosis induced by a decrease in NF-kappa B pathway activation. The NF-kappa B signaling pathway plays an important role in this process. Therefore, combining GA and celastrol may be a promising modality for treating oral squamous cell carcinoma.
背景
藤黄酸（GA）是藤黄的主要活性成分，藤黄是一种广泛使用的传统中药，已被报道具有对抗某些恶性肿瘤的强大细胞毒性作用。许多研究表明，NF-κB 信号通路在化疗过程中肿瘤细胞的抗凋亡和耐药性中发挥重要作用。在这项研究中，研究了 GA 和 NF-κB 抑制剂雷公藤红素对口腔癌细胞的作用和机制。
方法
用 GA 单独、雷公藤红素单独或 GA 加雷公藤红素处理三种人口腔鳞状细胞癌细胞系 Tca8113、TSCC 和 NT。通过 MTT 测定评估细胞毒性。通过 Annexin V/PI 染色以及 Tca8113 细胞中的透射电子显微镜检查观察细胞凋亡率。通过免疫荧光测定和体外核提取物和电泳迁移率变动分析（EMSA）测定口腔鳞状细胞癌细胞系中组成型 NF-κB 活性的水平。为了进一步研究 NF-κB 活性在 GA 和雷公藤红素处理口腔鳞状细胞癌中的作用，我们使用显性负突变体 SR-IκBα抑制 NF-κB 活性，并观察其对 GA 作用的影响。
结果
结果表明，GA 可抑制口腔鳞状细胞癌细胞系的增殖并诱导其凋亡，并且 GA 处理同时激活 NF-κB 途径。雷公藤红素的最小细胞毒性剂量能够有效地抑制 GA 诱导的 NF-κB 途径激活。在用 GA 和雷公藤红素的最小细胞毒性剂量或显性负突变体 SR-IκBα联合处理后，增殖明显受到抑制，Tca8113 细胞的凋亡率明显增加。
结论
GA 和雷公藤红素联合具有协同抗肿瘤作用。这种作用主要归因于 NF-κB 途径激活减少诱导的凋亡。NF-κB 信号通路在这个过程中起重要作用。因此，联合使用 GA 和雷公藤红素可能是治疗口腔鳞状细胞癌的一种有前途的方法。
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