Colon cancer is a disease with a high prevalence rate worldwide, and for its treatment, a 5-fluorouracil (5-FU)-based chemotherapeutic strategy is generally used. However, conventional anticancer agents have some limitations, including the development of drug resistance. Therefore, there has recently been a demand for the improvement of antitumor agents using natural products with low side effects and high efficacy. Polydatin is a natural active compound extracted from an annual plant, and widely known for its anticancer effects in diverse types of cancer. However, it is still not clearly understood how polydatin ameliorates several drawbacks of standard anticancer drugs by reinforcing the chemosensitivity against 5-FU, and neither are the intrinsic mechanisms behind this process. In this study, we examined how polydatin produces anticancer effects in two types of colon cancer, called HCT116 and HT-29 cells. Polydatin has the ability to repress the progression of colon cancer, and causes a modification of distribution in the cell cycle by a flow cytometry analysis. It also induces mitochondrial dysfunctions through oxidative stress and the loss of mitochondrial membrane potential. The present study investigated the apoptosis caused by the disturbance of calcium regulation and the expression levels of related proteins through flow cytometry and immunoblotting analysis. It was revealed that polydatin suppresses the signaling pathways of the mitogen-activated protein kinase (MAPK) and PI3K/AKT. In addition, it was shown that polydatin combined with 5-FU counteracts drug resistance in 5-FU-resistant cells. Therefore, this study suggests that polydatin has the potential to be developed as an innovative medicinal drug for the treatment of colon cancer.

中文翻译：

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虎杖苷通过在结肠癌中通过钙内流增强细胞凋亡来抵消 5-氟尿嘧啶耐药性

结肠癌是一种全球患病率很高的疾病，其治疗通常采用基于5-氟尿嘧啶（5-FU）的化疗策略。然而，传统的抗癌药物有一些局限性，包括耐药性的发展。因此，近来需要使用副作用低且功效高的天然产物来改进抗肿瘤剂。虎杖苷是一种从一年生植物中提取的天然活性化合物，因其对多种癌症的抗癌作用而广为人知。然而，仍然不清楚虎杖苷如何通过增强对 5-FU 的化学敏感性来改善标准抗癌药物的几个缺点，而且这个过程背后的内在机制也不是。在这项研究中，我们研究了虎杖苷如何在两种类型的结肠癌中产生抗癌作用，称为 HCT116 和 HT-29 细胞。虎杖苷具有抑制结肠癌进展的能力，并通过流式细胞术分析导致细胞周期分布的改变。它还通过氧化应激和线粒体膜电位的丧失诱导线粒体功能障碍。本研究通过流式细胞术和免疫印迹分析研究了钙调节紊乱引起的细胞凋亡和相关蛋白的表达水平。结果表明，虎杖苷抑制丝裂原活化蛋白激酶 (MAPK) 和 PI3K/AKT 的信号通路。此外，还表明虎杖苷与 5-FU 结合可抵消 5-FU 耐药细胞的耐药性。所以，