The NF-kappa B inhibitor, celastrol, could enhance the anti-cancer effect of gambogic acid on oral squamous cell carcinoma.
The NF-kappa B inhibitor, celastrol, could enhance the anti-cancer effect of gambogic acid on oral squamous cell carcinoma.
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NF-κB抑制剂雷公藤红素可增强藤黄酸对口腔鳞状细胞癌的抗癌作用
DOI：
10.1186/1471-2407-9-343
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发表时间：
2009-09-25
期刊：
影响因子：
3.8
通讯作者：
Chen W
中科院分区：
文献类型：
--
作者：
He D;Xu Q;Yan M;Zhang P;Zhou X;Zhang Z;Duan W;Zhong L;Ye D;Chen W
背景藤黄酸（gambogic acid， GA）是一种广泛应用的中药藤黄的主要活性成分，据报道，它是一种有效的细胞毒剂，可以治疗一些恶性肿瘤。许多研究表明，NF-kappa B信号通路在化疗过程中肿瘤细胞的抗凋亡和耐药中起着重要作用。本研究探讨了GA和nf - κ B抑制剂celastrol对口腔癌细胞的作用及其机制。方法分别用GA单用、celastrol单用或GA加celastrol治疗3株人口腔鳞状细胞癌Tca8113、TSCC和NT。MTT法测定细胞毒性。采用膜联蛋白V/PI染色及透射电镜观察Tca8113细胞凋亡率。采用体外免疫荧光法、核提取物法和电泳迁移位移法（EMSAs）检测口腔鳞癌细胞株组成型nf - κ B活性水平。为了进一步研究NF-kappa B活性在GA和celastrol治疗口腔鳞状细胞癌中的作用，我们使用显性阴性突变体SR-IκBα抑制NF-kappa B活性，并观察其对GA疗效的影响。结果GA对口腔鳞状细胞癌细胞具有抑制增殖和诱导凋亡的作用，同时激活nf - κ B通路。最小剂量的雷公藤红素能够有效抑制ga诱导的NF-kappa B通路的激活。GA与最小细胞毒剂量的celastrol或显性阴性突变体sr - i - κ b α联合处理后，Tca8113细胞增殖明显受到抑制，凋亡率明显升高。结论赤霉素与雷公藤红素联用具有协同抗肿瘤作用。这种作用主要归因于nf - κ B通路激活减少引起的细胞凋亡。NF-kappa B信号通路在这一过程中起重要作用。因此，GA联合celastrol可能是治疗口腔鳞状细胞癌的一种有前景的治疗方式。
BackgroundGambogic 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.MethodsThree 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-IκBα to inhibit NF-kappa B activity and to observe its influence on the effect of GA.ResultsThe 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-IκBα, proliferation was significantly inhibited, and the apoptotic rate of Tca8113 cells was significantly increased.ConclusionThe 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.
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影响因子：
15.9
作者：
Baldwin, AS
通讯作者：
Baldwin, AS
DOI：
10.1002/hed.20437
发表时间：
2006-10-01
影响因子：
2.9
作者：
Bindhu, O. S.;Ramadas, K.;Pillai, M. Radhakrishna
通讯作者：
Pillai, M. Radhakrishna
影响因子：
11.2
作者：
Yang, Huanjie;Chen, Di;Dou, Q. Ping
通讯作者：
Dou, Q. Ping
影响因子：
56.9
作者：
Wang, CY;Mayo, MW;Baldwin, AS
通讯作者：
Baldwin, AS
影响因子：
5.4
作者：
Panthong, Ampai;Norkaew, Pinpaka;Reutrakul, Vichai
通讯作者：
Reutrakul, Vichai