Abstract：
Actin filaments form unique structures with robust actin bundles and cytoskeletal networks affixed to the extracellular matrix and interact with neighboring cells, which are crucial structures for cancer cells to acquire a motile phenotype. This study aims to investigate a novel antitumor mechanism by which Tanshinone IIA (Tan IIA) modulates the morphology and migration of liver cancer cells via actin cytoskeleton regulation. 97H and Huh7 exhibited numerous tentacle-like protrusions that interacted with neighboring cells. Following treatment with Tan IIA, 97H and Huh7 showed a complete absence of cytoplasmic protrusion and adherens junctions, thereby effectively impeding their migration capability. The fluorescence staining of F-actin and microtubules indicated that these tentacle-like protrusions and cell-cell networks were actin-based structures that led to morphological changes after Tan IIA treatment by retracting and reorganizing beneath the membrane. Tan IIA can reverse the actin depolymerization and cell morphology alterations induced by latrunculin A. Tan IIA down-regulated actin and Rho GTPases expression significantly, as opposed to inducing Rho signaling activation. Preventing the activity of proteasomes and lysosomes had no discernible impact on the modifications in cellular structure and protein expression induced by Tan IIA. However, as demonstrated by the puromycin labeling technique, the newly synthesized proteins were significantly inhibited by Tan IIA. In conclusion, Tan IIA can induce dramatic actin cytoskeleton remodeling by inhibiting the protein synthesis of actin and Rho GTPases, resulting in the suppression of tumor growth and migration. Targeting the actin cytoskeleton of Tan IIA is a promising strategy for HCC treatment.
摘要：
肌动蛋白丝形成独特的结构，具有固定在细胞外基质上的强大的肌动蛋白束和细胞骨架网络，并与相邻细胞相互作用。它们是癌细胞获得活动表型的关键结构。本研究旨在探讨一种新的抗肿瘤机制，丹参酮IIA（TanIIA）通过肌动蛋白细胞骨架调节调节肝癌细胞的形态和迁移。97H和Huh7表现出许多与相邻细胞相互作用的触手状突起。用TanIIA治疗后，97H和Huh7显示完全没有细胞质突出和粘附连接，从而有效地阻碍了他们的迁移能力。F-肌动蛋白和微管的荧光染色表明，这些触手状突起和细胞-细胞网络是基于肌动蛋白的结构，在TanIIA处理后，通过在膜下缩回和重组导致形态变化。TanIIA可以逆转LatrunculinA诱导的肌动蛋白解聚和细胞形态改变。TanIIA显著下调肌动蛋白和RhoGTP酶的表达，与诱导Rho信号激活相反。防止蛋白酶体和溶酶体的活性对TanIIA诱导的细胞结构和蛋白质表达的修饰没有明显的影响。然而,正如嘌呤霉素标记技术所证明的那样，新合成的蛋白质被TanIIA显著抑制。总之,TanIIA可以通过抑制肌动蛋白和RhoGTPases的蛋白质合成来诱导显著的肌动蛋白细胞骨架重塑，从而抑制肿瘤的生长和迁移。靶向TanIIA的肌动蛋白细胞骨架是HCC治疗的有希望的策略。
