PO.TB07.02 · 肿瘤生物学
高良姜素通过敲低TINCR表达有效抑制肝癌干细胞的增殖和干性特征
Galangin effectively inhibits the proliferation and stemness characteristics of liver cancer stem cells by knocking down the expression of TINCR.
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摘要 Abstract
中文摘要
肝细胞癌(HCC)是全球癌症相关死亡的主要原因之一。肝癌干细胞(LCSCs)被认为在其病理过程中发挥关键作用，但其在HCC中的机制仍知之甚少。TINCR(终末分化诱导长非编码RNA)影响包括HCC在内多种恶性肿瘤中的癌细胞行为。近期研究强调了天然抗癌剂尤其是高良姜素(GLN)的潜力。该化合物以其抗菌、抗真菌和抗病毒特性而著称，还可能有助于控制高血压、糖尿病等疾病并用于癌症预防。然而，GLN对HCC的具体作用仍未完全明确。本研究旨在探讨GLN对TINCR表达的分子机制和抗癌特性，而TINCR可能影响肝癌干细胞(LCSCs)的干性特征。我们的研究结果表明TINCR在LCSCs中高表达，提示其对维持这些细胞的干性特性和肿瘤发生至关重要。在Wst-1实验中，GLN处理表现出对增殖的剂量依赖性抑制效应，并在LCSCs中诱导显著的形态学变化，提示在处理24小时后诱导了凋亡。此外，与对照相比，GLN处理24小时后TINCR的表达受到显著抑制。进行了Western blot分析和qRT-PCR以评估致癌信号通路，包括beta-catenin、mTOR和STAT3及其下游靶点。我们的结果表明，GLN处理联合TINCR敲低后，细胞活力和致癌信号以及LCSC干性标志物均显著降低，提示在GLN处理的同时抑制TINCR表达能有效破坏致癌信号并抑制LCSC干性特征。此外，TINCR敲低显著增强了抗增殖效应和对多柔比星(Doxorubicin)的敏感性。我们的数据将GLN引入为一种有前景的、天然且无毒的抗癌化合物，展示了其通过调控TINCR表达模式治疗HCC的治疗潜力。
查看英文原文 English abstract
Hepatocellular carcinoma (HCC) is a leading cause of cancer-related deaths worldwide. Liver cancer stem cells (LCSCs) are thought to play a crucial role in its pathology, but their mechanisms in HCC remain poorly understood. TINCR (terminal differentiation-induced long non-coding RNA) influences cancer cell behavior in various malignancies, including HCC. Recent research has highlighted the potential of natural anticancer agents, particularly Galangin (GLN). This compound is recognized for its antibacterial, antifungal, and antiviral properties, and it may also contribute to managing conditions like hypertension, diabetes, and cancer prevention. However, the specific effects of GLN on HCC are still not fully understood. The present study aims to explore the molecular mechanism and anticancer properties of GLN on TINCR expression, which may influence the stemness characteristics of liver cancer stem cells (LCSCs). Our findings demonstrate that TINCR is highly expressed in LCSCs, suggesting that it is essential for maintaining the stemness properties and tumorigenesis of these cells. In the Wst-1 assay, GLN treatment exhibited a dose-dependent inhibitory effect on proliferation and induced significant morphological changes in LCSCs, indicative of apoptosis induction after 24 h of treatment. Furthermore, the expression of TINCR was significantly inhibited after 24 h of GLN treatment compared to the control. Western blot analysis and qRT-PCR were conducted to assess oncogenic signaling pathways, including beta-catenin, mTOR, and STAT3, along with downstream targets. Our results indicated a significant reduction in cell viability and oncogenic signals, as well as in LCSC stemness markers, following GLN treatment combined with TINCR knockdown, suggesting that inhibiting TINCR expression alongside GLN treatment effectively disrupts oncogenic signals and inhibits LCSC stemness characteristics. In addition, TINCR knockdown significantly enhanced the antiproliferative effects and sensitivity to Doxorubicin. Our data introduce GLN as a promising, natural, and non-toxic anticancer compound, demonstrating its therapeutic potential for treating HCC by regulating the expression pattern of TINCR.
利益披露 Disclosure
A. S. Fyala, None..
M. M. Elkewedi, None..
A. S. Sultan, None.