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Resveratrol inhibits human leiomyoma cell proliferation via crosstalk between integrin αvβ3 and IGF-1R
Food and Chemical Toxicology ( IF 4.3 ) Pub Date : 2018-07-17 , DOI: 10.1016/j.fct.2018.07.030
Yih Ho , Yu-Chen SH Yang , Yu-Tang Chin , Szu-Yi Chou , Yi-Ru Chen , Ya-Jung Shih , Jacqueline Whang-Peng , Chun A. Changou , Hsuan-Liang Liu , Shwu-Jiuan Lin , Heng-Yuan Tang , Hung-Yun Lin , Paul J. Davis

Leiomyomas (myomas) are the most common benign smooth muscle cell tumor of the myometrium. Resveratrol, a stilbene, has been used as an anti-inflammatory and antitumor agent. In the current study, we investigated the inhibitory effect of resveratrol on the proliferation of primary human myoma cell cultures. Resveratrol arrested cell proliferation via integrin αvβ3. It also inhibited integrin αvβ3 expression and protein accumulation. Concurrently, constitutive AKT phosphorylation in myoma cells was inhibited by resveratrol. Expressions of proapoptotic genes, such as cyclooxygenase (COX)-2, p21 and CDKN2, were induced by resveratrol in myoma cells. On the other hand, expressions of proliferative (anti-apoptotic) genes were either inhibited, as in BCL2, or unchanged, as in cyclin D1 and proliferating cell nuclear antigen (PCNA). The accumulation of insulin-like growth factor (IGF)-1 receptor (IGF-1R) was inhibited by resveratrol in primary myoma cells. IGF-1-induced cell proliferation was inhibited by co-incubation with resveratrol. Therefore, growth modulation of myoma cells occurs via mechanisms dependent on cross-talk between integrin αvβ3 and IGF-1R. Our findings suggest that resveratrol can be considered an alternative therapeutic agent for myomas.



中文翻译:

白藜芦醇通过整合素αvβ3与IGF-1R之间的串扰抑制人平滑肌细胞增殖

平滑肌瘤(肌瘤)是子宫肌层最常见的良性平滑肌细胞瘤。白藜芦醇,一种二苯乙烯,已被用作抗炎和抗肿瘤剂。在当前的研究中,我们研究了白藜芦醇对原代人肌瘤细胞培养物增殖的抑制作用。白藜芦醇通过整联蛋白αvβ3阻止细胞增殖。它还抑制了整联蛋白αvβ3的表达和蛋白质的积累。同时,白藜芦醇抑制肌瘤细胞中的组成性AKT磷酸化。凋亡基因的表达,例如环氧合酶(COX)-2p21CDKN2,是由白藜芦醇在肌瘤细胞中诱导的。另一方面,增生(抗凋亡)基因的表达被抑制,如在BCL2中,或被抑制,如在细胞周期蛋白D1和增殖细胞核抗原(PCNA)中。白藜芦醇可抑制原发性肌瘤细胞中胰岛素样生长因子(IGF)-1受体(IGF-1R)的积累。与白藜芦醇共孵育可抑制IGF-1诱导的细胞增殖。因此,肌瘤细胞的生长调节通过依赖于整联蛋白αvβ3和IGF-1R之间的串扰的机制发生。我们的发现表明白藜芦醇可以被认为是肌瘤的替代治疗剂。

更新日期:2018-07-17
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