Feng Jianyu, Jin Yiyi, Peng Jun, Wei Lihui, Cai Qiaoyan, Yan Zhaokun, Lai Zijun, Lin Jiumao
Biomedical Research Center of Academy of Integrative Medicine of Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian 350122, P.R. China.
Fujian Key Laboratory of Integrative Medicine on Geriatrics, Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian 350122, P.R. China.
Oncol Lett. 2017 Dec;14(6):8197-8205. doi: 10.3892/ol.2017.7244. Epub 2017 Oct 20.
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. (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 and . 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.
结直肠癌(CRC)的发生与多种细胞内信号转导级联反应的失衡密切相关,包括蛋白激酶B(AKT)、丝裂原活化蛋白激酶1(MAPK)、信号转导和转录激活因子3(STAT3),以及这些信号网络之间的相互作用。目前,抗肿瘤药物往往是单靶点的,因此并不总是具有治疗效果。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。这些问题凸显了开发新型、更有效的抗癌药物的迫切需求。华蟾素(HDW)已被用作治疗结直肠癌的传统中药的主要成分,不良反应数量有限。然而,其抗癌活性的分子机制仍需进一步阐明。在本研究中,使用异种移植模型和各种不同的人CRC细胞系,评估了华蟾素乙醇提取物(EEHDW)对肿瘤生长的疗效,并研究了其潜在的分子作用机制。结果表明,EEHDW能够抑制癌症生长。此外,EEHDW能够抑制几种与CRC相关的信号通路的激活,并能够调节各种炎症和血管生成因子的表达。这导致了细胞凋亡的诱导、细胞增殖的抑制以及肿瘤血管生成的抑制。本研究表明,EEHDW能够表现出抗癌活性,因为它能够影响多个细胞内靶点,这表明它可能是一种治疗结直肠癌的新型多效治疗剂。