Department of Pharmacy, The People's Hospital of Guangxi Zhuang Autonomous Region, Nanning, Guangxi, 530021, People's Republic of China.
Department of Radiation Oncology of the Clinical Cancer Center, The People's Hospital of Guangxi Zhuang Autonomous Region, Nanning, Guangxi, 530021, People's Republic of China.
Biomed Pharmacother. 2020 Apr;124:109835. doi: 10.1016/j.biopha.2020.109835. Epub 2020 Jan 17.
Epidemiologically, the disease incidence of colorectal cancer (CRC) ranks the third among all malignant tumors, and its mortality is the second following lung cancer. If unmanaged, CRC will develop fatal invasiveness and metastasis. However, existing chemotherapy is limitedly effective to treat metastatic CRC. Genistein, a functional phytoestrogen, is found with potent pharmacological activity against cancer cells. Therefore, this study was designed to characterize the clinical signatures of human CRC and to conduct anti-CRC experiments using genistein.
Briefly, the plasma, tumor, non-tumor samples of CRC patients were harvested for biological experiments, followed by analysis of clinical data. A pharmacological study in vitro of genistein for treating CRC cells was conducted accordingly.
In diagnostic data, molecular tumor biomarkers in CRC patients were detected in plasma samples, consistent with pathological and imaging diagnoses of CRC. Notably, carcinomatous expressions of miR-95, serum glucocorticoid kinase 1 (SGK1), B-cell lymphoma-2 (Bcl-2), extracellular regulated protein kinase 1 (Erk1) in human CRC were notably elevated when compared to those in non-tumor controls. In pharmacological experiments using cell culture model, genistein-treated CRC cells resulted in reduced cellular viability, elevated lactate dehydrogenase (LDH) content, increased apoptotic cells and TdT mediated dUTP nick end labeling (TUNEL)-positive cells following a dose-dependent manner. Interestingly, down-regulated expressions of endogenous miR-95, SGK1, Bcl-2, Erk1 were observed after genistein treatments in a dose-dependent way.
Collectively, the current clinical data indicate pathological markers of miR-95, SGK1, Erk1 in human CRC cases, and further experimental findings reveal that anti-CRC pharmacological mechanism using genistein was implicated in suppression of cellular miR-95, SGK1, Erk1 expressions. Together, genistein may be a promising bioactive compound for treating CRC.
从流行病学角度来看，结直肠癌（CRC）的发病率在所有恶性肿瘤中排名第三，其死亡率仅次于肺癌。如果不加以治疗，CRC 会发展为致命的侵袭性和转移性。然而，现有的化疗对转移性 CRC 的治疗效果有限。染料木黄酮是一种功能性植物雌激素，具有很强的抗癌细胞药理学活性。因此，本研究旨在描述人 CRC 的临床特征，并使用染料木黄酮进行抗 CRC 实验。
简要地说，从 CRC 患者的血浆、肿瘤、非肿瘤样本中采集生物实验样本，然后分析临床数据。相应地进行了体外染料木黄酮治疗 CRC 细胞的药理学研究。
在诊断数据中，在血浆样本中检测到 CRC 患者的分子肿瘤生物标志物，与 CRC 的病理和影像学诊断一致。值得注意的是，与非肿瘤对照相比，人 CRC 中 miR-95、血清糖皮质激素激酶 1（SGK1）、B 细胞淋巴瘤-2（Bcl-2）、细胞外调节蛋白激酶 1（Erk1）的癌变表达明显升高。在细胞培养模型的药理学实验中，染料木黄酮处理的 CRC 细胞导致细胞活力降低、乳酸脱氢酶（LDH）含量升高、凋亡细胞增加以及 TUNEL 阳性细胞增加，呈剂量依赖性。有趣的是，在剂量依赖性方式下，在用染料木黄酮处理后观察到内源性 miR-95、SGK1、Bcl-2、Erk1 的表达下调。
总的来说，目前的临床数据表明 miR-95、SGK1、Erk1 是 CRC 病例的病理标志物，进一步的实验结果表明，使用染料木黄酮的抗 CRC 药理机制涉及抑制细胞 miR-95、SGK1、Erk1 的表达。总之，染料木黄酮可能是治疗 CRC 的一种有前途的生物活性化合物。
