PLoS One：姜黄素抗小细胞肺癌机制

姜黄(Curcuma longa)是姜科植物姜黄的根茎，姜黄不仅在印度作为香料用于食品咖喱中，而且在中国具有悠久的药用历史，其性味辛、苦、温,可行气破瘀、通经止痛。姜黄主要成分姜黄素具有广泛的药理作用，而对于姜黄素抗肿瘤作用的研究，长期以来主要集中在肿瘤的化学预防方面。随着现代分子生物学研究的不断发展，研究者们对姜黄素作用机制有了更深入的研究。

虽然已有大量文献证实姜黄素可以防止癌变，抑制肿瘤的发展。然而，很少有人知道姜黄素的抗小细胞肺癌（SCLC）的具体机制。近日刊登在PLoS One杂志上的一项研究证实：姜黄素可以通过抑制STAT3的表达，进而抑制小细胞肺癌细胞增殖、影响肿瘤细胞的细胞周期，降低细胞迁移、侵袭和血管生成。

小细胞肺癌细胞经15μmol/ L的姜黄素处理后，姜黄素能有效抑制STAT3的磷酸化，下调STAT3的下游调控蛋白，这有助于抑制细胞的增殖，细胞集落形成能力减弱，细胞迁移和侵袭能力也降低。

姜黄素抑制增殖蛋白（Survivin、BCL-X和Cyclin B1）、VEGF、MMP-2，MMP-7和ICAM-1的表达。siRNA沉默STAT3的表达也能降低肿瘤细胞体外侵袭能力。相比之下，白细胞介素6（IL-6）激活STAT3增加细胞增殖，促进细胞的存活，血管生成、侵袭、迁移和肿瘤的生长也升高。

研究人员得出的结论是姜黄素是一种具有抑制STAT3活性的药物，姜黄素可能作为一种有效的治疗或预防小细胞肺癌的潜在药物。

doi:10.1371/journal.pone.0037960
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Curcumin Blocks Small Cell Lung Cancer Cells Migration, Invasion, Angiogenesis, Cell Cycle and Neoplasia through Janus Kinase-STAT3 Signalling Pathway.

Yang CL, Liu YY, Ma YG, Xue YX, Liu DG, Ren Y, Liu XB, Li Y, Li Z.

Curcumin, the active component of turmeric, has been shown to protect against carcinogenesis and prevent tumor development. However, little is known about its anti-tumor mechanism in small cell lung cancer (SCLC). In this study, we found that curcumin can inhibit SCLC cell proliferation, cell cycle, migration, invasion and angiogenesis through suppression of the STAT3. SCLC cells were treated with curcumin (15 µmol/L) and the results showed that curcumin was effective in inhibiting STAT3 phosphorylation to downregulate of an array of STAT3 downstream targets ,which contributed to suppression of cell proliferation, loss of colony formation, depression of cell migration and invasion. Curcumin also suppressed the expression of proliferative proteins (Survivin, Bcl-X(L) and Cyclin B1), and invasive proteins (VEGF, MMP-2, MMP-7 and ICAM-1).Knockdown of STAT3 expression by siRNA was able to induce anti-invasive effects in vitro. In contrast, activation of STAT3 upstream of interleukin 6 (IL-6) leads to the increased cell proliferation ,cell survival, angiogenesis, invasion, migration and tumor growth. Our findings illustrate the biologic significance of IL-6/JAK/STAT3 signaling in SCLC progression and providenovel evidence that the pathway may be a new potential target for therapy of SCLC. It was concluded that curcumin is a potent agent in the inhibition of STAT3 with favorable pharmacological activity,and curcumin may have translational potential as an effective cancer therapeutic or preventive agent for SCLC.