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The NF-kappa B inhibitor, celastrol, could enhance the anti-cancer effect of gambogic acid on oral squamous cell carcinoma

文献类型：期刊论文

作者He, Di1,2; Xu, Qin2,3,4; Yan, Ming2,3,4; Zhang, Ping2,3,4; Zhou, Xiaojian2,3,4; Zhang, Zhiyuan2,3,4; Duan, Wenhu5; Zhong, Laiping2; Ye, Dongxia3,4; Chen, Wantao2,3,4
刊名BMC CANCER
出版日期2009-09-25
卷号9
ISSN号1471-2407
DOI10.1186/1471-2407-9-343
文献子类Article
英文摘要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-I kappa B alpha 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-I kappa B alpha, 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.
WOS关键词GARCINIA-HANBURYI ; NUDE-MICE ; ACTIVATION ; APOPTOSIS ; RESISTANCE ; TRITERPENE ; PRODUCTS ; PROTEIN ; KINASE ; GROWTH
资助项目National Natural Science Foundation of China[30330580] ; National Natural Science Foundation of China[30973343] ; Project of the Shanghai Science and Technology Committee[08JC1414400] ; Project of the Shanghai Science and Technology Committee[09431902200] ; Shanghai Leading Academic Discipline Project[S30206]
WOS研究方向Oncology
语种英语
WOS记录号WOS:000271124600001
出版者BMC
源URL[http://119.78.100.183/handle/2S10ELR8/279123]  
专题药物化学研究室
通讯作者Chen, Wantao
作者单位1.Zhejiang Univ, Dept Oral & Maxillofacial Surg, Affiliated Hosp 2, Sch Med, Hangzhou 310009, Zhejiang, Peoples R China
2.Shanghai Jiao Tong Univ, Dept Oral & Maxillofacial Surg, Coll Stomatol, Sch Med,Peoples Hosp 9, Shanghai 200011, Peoples R China;
3.Shanghai Key Lab Stomatol, Lab Oral Tumor & Oral Biol, Shanghai 200011, Peoples R China;
4.Shanghai Res Inst Stomatol, Shanghai 200011, Peoples R China;
5.Chinese Acad Sci, Dept Med Chem, Shanghai Inst Mat Med, Shanghai 201203, Peoples R China;
推荐引用方式
GB/T 7714		 He, Di,Xu, Qin,Yan, Ming,et al. The NF-kappa B inhibitor, celastrol, could enhance the anti-cancer effect of gambogic acid on oral squamous cell carcinoma[J]. BMC CANCER,2009,9.
APA He, Di.,Xu, Qin.,Yan, Ming.,Zhang, Ping.,Zhou, Xiaojian.,...&Chen, Wantao.(2009).The NF-kappa B inhibitor, celastrol, could enhance the anti-cancer effect of gambogic acid on oral squamous cell carcinoma.BMC CANCER,9.
MLA He, Di,et al."The NF-kappa B inhibitor, celastrol, could enhance the anti-cancer effect of gambogic acid on oral squamous cell carcinoma".BMC CANCER 9(2009).

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来源：上海药物研究所

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