Department of Abdominal Surgery, Zhejiang Cancer Hospital, Hangzhou 310022, China.
Med Hypotheses. 2013 Oct;81(4):653-5. doi: 10.1016/j.mehy.2013.06.034. Epub 2013 Jul 30.
The long-term prognosis of hepatocellular carcinoma (HCC) remains unsatisfactory even after surgical resection and chemoembolization because of a high recurrence rate. However, fewer agents are currently available to block or postpone HCC progression. Recent studies show that the activation of toll-like receptor 4 (TLR4)-NF-kappaB(NF-κB) signaling pathway can lead to the expression of interleukin (IL)-1, IL-6, IL-10, nitric oxide (NO) and tumor necrosis factor (TNF)-α, and promote chronic liver inflammation and malignant tumor development. A new small molecule TAK-242 (Resatorevid) can selectively inhibit TLR4-mediated signaling pathway and suppress the expression of inflammatory mediators. But the researches have not been reported whether TAK-242 can inhibit liver tumor growth and invasion. So it suggested a new hypothesis that TAK-242 selectively blocks the TLR4-NF-κB pathway and is hoped to be a potential and creative drug for preventing invasion and metastasis of HCC.
即使在接受手术切除和化疗栓塞治疗后，肝细胞癌 (HCC) 的长期预后仍然不尽如人意，因为其复发率很高。然而，目前可用的药物较少能够阻止或延缓 HCC 的进展。最近的研究表明，Toll 样受体 4 (TLR4)-NF-κB (NF-κB) 信号通路的激活可导致白细胞介素 (IL)-1、IL-6、IL-10、一氧化氮 (NO) 和肿瘤坏死因子 (TNF)-α 的表达，并促进慢性肝炎症和恶性肿瘤的发展。一种新的小分子 TAK-242 (Resatorevid) 可以选择性地抑制 TLR4 介导的信号通路并抑制炎症介质的表达。但目前还没有关于 TAK-242 是否能抑制肝肿瘤生长和侵袭的研究报道。因此，提出了一个新的假设，即 TAK-242 选择性地阻断 TLR4-NF-κB 途径，有望成为预防 HCC 侵袭和转移的一种有潜力和创造性的药物。
