Hedyotis diffusa willd extract suppresses colorectal cancer growth through multiple cellular pathways
Hedyotis diffusa willd extract suppresses colorectal cancer growth through multiple cellular pathways
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DOI：
10.3892/ol.2017.7244
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发表时间：
2017-12-01
期刊：
影响因子：
2.9
通讯作者：
Lin, Jiumao
中科院分区：
文献类型：
--
作者：
Feng, Jianyu;Jin, Yiyi;Lin, Jiumao
结直肠癌（CRC）的发生与细胞内多种信号转导通路的失衡密切相关，包括蛋白激酶B（AKT）、丝裂原活化蛋白激酶1（MAPK）、信号转导子和转录激活子3（STAT 3）以及这些信号网络之间的串扰。目前，抗肿瘤剂通常是单靶向的，因此并不总是治疗有效的。此外，长期使用这些抗肿瘤药物往往会产生耐药性和潜在的副作用。这些问题突出了开发新的和更有效的抗癌药物的迫切需要。白花蛇舌草作为传统中药治疗大肠癌的主要成分，其不良反应较少。然而，其抗癌活性的分子机制仍需要进一步阐明。在本研究中，使用异种移植模型和各种不同的人CRC细胞系，评价了HDW乙醇提取物（EEHDW）对肿瘤生长的功效，并研究了其潜在的分子作用机制。结果表明，EEHDW能够抑制体内和体外肿瘤生长。此外，EEHDW能够抑制几种CRC相关信号通路的激活，并能够调节各种炎症和血管生成因子的表达。这导致诱导细胞凋亡和抑制细胞增殖以及肿瘤血管生成。目前的研究表明，EEHDW是能够表现出抗癌活性，由于其能够影响多个细胞内的目标，这表明它可能是一个新的多功能治疗剂用于治疗结直肠癌。
The development of colorectal cancer (CRC) is strongly associated with the imbalance of various intracellular signal transduction cascades, including protein kinase B (AKT), mitogen-activated protein kinase 1 (MAPK), signal transducer and activator of transcription 3 (STAT3), as well as crosstalk between these signaling networks. At present, anti-tumor agents are often single-targeted and therefore are not always therapeutically effective. Moreover, long-term use of these anti-tumor agents often generates drug resistance and potential side effects. These problems highlight the urgent need for the development of novel and more effective anti-cancer drugs. Hedyotis diffusa Willd (HDW) has been used as a major component in traditional Chinese medicine for the clinical treatment of colorectal cancer, with a limited number of adverse effects. However, the molecular mechanisms, which underlie its anti-cancer activity, still require further elucidation. In the present study, using xenograft models and various different human CRC cell lines, the efficacy of the ethanol extract of HDW (EEHDW) against tumor growth was evaluated, and its underlying molecular mechanisms of action were investigated. It was demonstrated that EEHDW was able to inhibit cancer growth in vivo and in vitro. Furthermore, EEHDW was able to suppress the activation of several CRC-associated signaling pathways and was able to regulate the expression of various inflammatory and angiogenic factors. This resulted in the induction of apoptosis and inhibition of cellular proliferation, as well as tumor angiogenesis. The present study demonstrated that EEHDW is able to exhibit anti-cancer activity due to its ability to affect multiple intracellular targets, which suggests that it may be a novel multi-potent therapeutic agent for the treatment of colorectal cancer.