Curcumin inhibits tumor growth and angiogenesis in ovarian carcinoma by targeting the nuclear factor-κB pathway
Curcumin inhibits tumor growth and angiogenesis in ovarian carcinoma by targeting the nuclear factor-κB pathway
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DOI：
10.1158/1078-0432.ccr-06-3072
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发表时间：
2007-06-01
影响因子：
11.5
通讯作者：
Sood, Anil K.
中科院分区：
文献类型：
--
作者：
Lin, Yvonne G.;Kunnumakkara, Ajaikumar B.;Sood, Anil K.
用途：姜黄素是姜黄的一种成分，已被证明在很大程度上通过抑制转录因子核因子-κ B（NF-κ B）来抑制炎症和血管生成。本研究评估姜黄素对卵巢癌生长的影响，使用原位小鼠模型卵巢cancer.Experimental Design：在体外和体内实验姜黄素与和没有多西他赛进行了使用人卵巢癌细胞系SKOV 3 ip 1，HeyA 8，HeyA 8-MDR在无胸腺小鼠。NF-κ B调节用电泳迁移率变动分析确定。评价血管生成细胞因子，细胞增殖（增殖细胞核抗原），血管生成（CD 31），和凋亡（末端脱氧核苷酸转移酶介导的dUTP缺口末端标记）进行了使用免疫组化analysis.Results：姜黄素抑制诱导型NF-κ B B激活和抑制增殖体外。体内剂量探索实验表明，500 mg/kg经口给药是抑制NF-κ B和信号转导和转录激活因子3激活以及降低血管生成细胞因子表达所需的最佳剂量。在SKOV 3 ip 1和HeyA 8体内模型中，与对照组相比，单独使用姜黄素导致平均肿瘤生长减少49%（P = 0.08）和55%（P = 0.01），而与多西他赛联合使用时，与对照组相比，平均肿瘤生长减少96%（P < 0.001）和77%。在患有多药耐药HeyA 8-MDR肿瘤的小鼠中，单独使用姜黄素和与多西他赛联合使用姜黄素分别导致肿瘤生长显著减少47%和58%（P = 0.05）。在SKOV 3 ip 1和HeyA 8肿瘤中，姜黄素单独或与多西他赛联合使用可降低肿瘤细胞增殖（P <0.001）和微血管密度（P < 0.001），并增加肿瘤细胞凋亡（P < 0.05）。结论：基于临床前模型的显著疗效，基于姜黄素的治疗可能对卵巢癌患者有吸引力。
Purpose: Curcumin, a component of turmeric, has been shown to suppress inflammation and angiogenesis largely by inhibiting the transcription factor nuclear factor-kappa B (NF-kappa B). This study evaluates the effects of curcumin on ovarian cancer growth using an orthotopic murine model of ovarian cancer.Experimental Design: In vitro and in vivo experiments of curcumin with and without docetaxel were done using human ovarian cancer cell lines SKOV3ip1, HeyA8, and HeyA8-MDR in athymic mice. NF-kappa B modulation was ascertained using electrophoretic mobility shift assay. Evaluation of angiogenic cytokines, cellular proliferation (proliferating cell nuclear antigen), angiogenesis (CD31), and apoptosis (terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling) was done using immunohistochemical analyses.Results: Curcumin inhibited inducible NF-kappa B activation and suppressed proliferation in vitro. In vivo dose-finding experiments revealed that 500 mg/kg orally was the optimal dose needed to suppress NF-kappa B and signal transducers and activators of transcription 3 activation and decrease angiogenic cytokine expression. In the SKOV3ip1 and HeyA8 in vivo models, curcumin alone resulted in 49% (P = 0.08) and 55% (P = 0.01) reductions in mean tumor growth compared with controls, whereas when combined with docetaxel elicited 96% (P < 0.001) and 77% reductions in mean tumor growth compared with controls. In mice with multidrug-resistant HeyA8-MDR tumors, treatment with curcumin alone and combined with docetaxel resulted in significant 47% and 58% reductions in tumor growth, respectively (P = 0.05). In SKOV3ip1 and HeyA8 tumors, curcumin alone and with docetaxel decreased both proliferation (P < 0.001) and microvessel density (P < 0.001) and increased tumor cell apoptosis (P < 0.05).Conclusions: Based on significant efficacy in preclinical models, curcumin-based therapies may be attractive in patients with ovarian carcinoma.