Capsaicin inhibits the metastasis of human papillary thyroid carcinoma BCPAP cells through the modulation of the TRPV1 channel.
Capsaicin inhibits the metastasis of human papillary thyroid carcinoma BCPAP cells through the modulation of the TRPV1 channel.
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DOI：
10.1039/c7fo01295k
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发表时间：
2018-01
期刊：
影响因子：
6.1
通讯作者：
Shichen Xu;Li Zhang;Xian Cheng;Huixin Yu;Jiandong Bao;Rongrong Lu
中科院分区：
文献类型：
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作者：
Shichen Xu;Li Zhang;Xian Cheng;Huixin Yu;Jiandong Bao;Rongrong Lu
辣椒素（Capsaicin，CAP）是一种有效的瞬时受体电位香草素1（TRPV 1）激动剂，是红辣椒的主要成分。近年来，辣椒素因其具有多种生物活性而受到越来越多的关注。然而，辣椒素对各种类型的癌症，特别是对甲状腺癌的抗癌作用尚未完全阐明。TRPV 1可以被辣椒素激活，在许多生物和生理过程中发挥关键作用。在本研究中，辣椒素对甲状腺乳头状癌BCPAP细胞的抗癌特性进行了研究。结果表明，TRPV 1和TRPV 6在不同类型的甲状腺细胞系中普遍表达。辣椒素可抑制BCPAP细胞的多步转移，而不影响细胞活力。辣椒素（25-100 μM）激活TRPV 1可显著抑制BCPAP细胞的迁移、侵袭和粘附。辣椒素处理后，EMT关键转录因子Snail 1和Twist 1蛋白水平呈剂量依赖性下降，下游E-cadherin蛋白表达上调。随后，辣椒素激活TRPV 1也引起MMP-2和MMP-9表达的显著抑制。此外，辣椒素对BCPAP细胞转移的抑制作用被TRPV 1特异性拮抗剂（辣椒素）的预处理所消除。我们的研究结果表明，辣椒素激活TRPV 1与甲状腺乳头状癌BCPAP细胞的转移抑制有关，表明靶向TRPV 1功能仍然是癌症治疗的可行策略。
Capsaicin (CAP), a potent transient receptor potential vanilloid type 1 (TRPV1) agonist, is a major ingredient of red pepper. Recently, capsaicin has attracted increasing attention owing to its multiple biological activities. However, the anticancer effects of capsaicin against various types of cancers, especially on thyroid carcinoma, have not been completely elucidated. TRPV1, which can be activated by capsaicin, plays a key role in many biological and physiological processes. In the present study, the anticancer properties of capsaicin against papillary thyroid cancer BCPAP cells were investigated. Our results indicated that TRPV1 and TRPV6 were universally expressed in different types of thyroid cell lines. Capsaicin could inhibit multiple steps of metastasis without affecting the viability of BCPAP cells. The activation of TRPV1 by capsaicin (25-100 μM) significantly suppressed the migration and invasion of BCPAP cells as well as their adhesion. The protein levels of Snail1 and Twist1, two critical EMT transcription factors (EMT-TFs), dramatically decreased in a dose-dependent manner after capsaicin treatment, accompanied by the up-regulation of downstream protein E-cadherin. Subsequently, the activation of TRPV1 by capsaicin also caused significant inhibition of the expression of MMP-2 and MMP-9. Moreover, the inhibitory effects of capsaicin on the metastasis of BCPAP cells were abrogated by the pre-treatment of a specific TRPV1 antagonist (capsazepin). Our results suggest that the activation of TRPV1 by capsaicin is associated with the metastatic inhibition of papillary thyroid cancer BCPAP cells, indicating that targeting of TRPV1 functions remains a feasible strategy for cancer treatment.