色甘酸对S100P与愤怒和交互的影响胰腺癌生长和小鼠模型的入侵。
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Arumugam T,拉马钱德兰V,洛格斯登CD
色甘酸对S100P与愤怒和交互的影响胰腺癌生长和小鼠模型的入侵。
中华肿瘤杂志,2006年12月20日,98 (24):1806 - 18。
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17179482 (在PubMed]
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背景:我们之前发现,S100P S100蛋白家族的一员,表示在90%以上的胰腺肿瘤与肿瘤生长和入侵。在目前的研究中,我们调查的能力antiallergy药物,色甘酸,阻止S100P函数。方法:色甘酸和S100P调查使用药物之间的相互作用关联列和通过检查色甘酸的影响coimmunoprecipitation S100P和晚期糖化终产物受体(愤怒)。色甘酸对细胞生长的影响、入侵和核factor-kappaB (NFkappaB)胰腺癌细胞的活动(BxPC-3和mpanc - 96)和没有(Panc-1)内源性S100P被细胞增殖试验研究,通过细胞入侵检测,分别通过荧光素酶报告基因分析。色甘酸在体内肿瘤生长的影响,研究了在三种原位模型(n = 20小鼠模型)的政府色甘酸(5毫克/公斤体重,日报)有或没有吉西他滨(125毫克/公斤体重,每周两次的),这种药物目前用于治疗胰腺癌。肿瘤生长被化验报告基因表达。统计测试都是双面的。结果:S100P保留色甘酸亲和柱。色甘酸封锁了coimmunoprecipitation S100P和愤怒。在体外,色甘酸(100 microM)抑制S100P-stimulated Panc-1细胞增殖(S100P意味着= 0.93 U,与S100P +色甘酸,意味着= 0.56 U,差异= 0.37 U; 95% confidence interval [CI] = 0.24 to 0.49 U; P = .001, n = 3), invasion (S100P, mean = 58.0%, versus S100P + cromolyn, mean = 9.4%, difference = 48.6%; 95% CI = 38.8% to 58.8%; P<.001, n = 3), and NFkappaB activity (S100P, mean = 14,460, versus S100P + cromolyn, mean = 7360 photons/s, difference = 7100 photons/s; 95% CI = 3689 to 10 510 photons/s; P = .005, n = 3). In vivo, cromolyn inhibited tumor growth in mice bearing tumor with endogenous S100P (BxPC-3: control, mean = 1.6 x 10(9) photons/s, versus cromolyn, mean = 4.4 x 10(8) photons/s, difference = 1.2 x 10(9) photons/s; 95% CI = 6.2 x 10(8) to 1.6 x 10(9) photons/s; P<.001, n = 5; MPanc-96: control, mean = 1.1 x 10(10) photons/s, versus cromolyn, mean = 4.8 x 10(9) photons/s, difference = 6.2 x 10(9) photons/s; 95% CI = 1.9 x 10(9) to 1.0 x 10(10) photons/s; P = .009, n = 5) and increased the effectiveness of gemcitabine (BxPC-3: gemcitabine, mean = 9.2 x 10(8) photons/s, versus combination, mean = 1.8 x 10(8) photons/s, difference = 7.4 x 10(8) photons/s; 95% CI = 4.5 x 10(8) to 1.0 x 10(9) photons/s; P<.001; MPanc-96: gemcitabine, mean = 4.1 x 10(9) photons/s, versus combination, mean = 2.0 x 10(9) photons/s, difference = 2.1 x 10(9) photons/s; 95% CI = 4.4 x 10(8) to 3.8 x 10(9) photons/s; P<.001). However, cromolyn had no effect on growth of tumors lacking S100P (Panc-1). CONCLUSION: Cromolyn binds S100P, prevents activation of RAGE, inhibits tumor growth, and increases the effectiveness of gemcitabine in experimental models.