PDF(Pubmed)
Abstract：
Indomethacin (INDO) has a mechanism of action based on inhibiting fatty acids cyclooxygenase activity within the inflammation process. The action mechanism could be correlated with possible anticancer activity, but its high toxicity in normal tissues has made therapy difficult. By the coprecipitation method, the drug carried in a layered double hydroxides (LDH) hybrid matrix would reduce its undesired effects by promoting chemotherapeutic redirection. Therefore, different samples containing INDO intercalated in LDH were synthesized at temperatures of 50, 70, and 90 °C and synthesis times of 8, 16, 24, and 48 h, seeking the best structural organization. X-ray diffraction (XRD), vibrational Fourier transform infrared spectroscopy (FT-IR), scanning electron microscopy (SEM), spectrophotometric analysis in UV-VIS, and differential thermogravimetric analysis (TGA/DTA) were used for characterization. Our results indicate that higher temperatures and longer synthesis time through coprecipitation reduce the possibility of INDO intercalation. However, it was possible to establish a time of 16 h and a temperature of 50 °C as the best conditions for intercalation. In vitro results confirmed the cell viability potential and anticancer activity in the LDH-INDO sample (16 h and 50 °C) for gastric cancer (AGP01, ACP02, and ACP03), breast cancer (MDA-MB-231 and MCF-7), melanoma (SK-MEL-19), lung fibroblast (MRC-5), and non-neoplastic gastric tissue (MN01) by MTT assay. Cell proliferation was inhibited, demonstrating higher and lower toxicity against MDA-MB-231 and SK-MEL-19. Thus, a clinical redirection of INDO is suggested as an integral and adjunctive anticancer medication in chemotherapy treatment.
摘要：
吲哚美辛（INDO）具有基于抑制炎症过程中脂肪酸环氧合酶活性的作用机制。其作用机制可能与可能的抗癌活性有关，但是它在正常组织中的高毒性使治疗变得困难。通过共沉淀法，在层状双氢氧化物（LDH）混合基质中携带的药物将通过促进化疗重定向来减少其不期望的作用。因此,在50、70和90°C的温度和8、16、24和48小时的合成时间合成了包含插入LDH的INDO的不同样品，寻求最佳的结构组织。X射线衍射(XRD)振动傅里叶变换红外光谱(FT-IR),扫描电子显微镜（SEM），紫外可见分光光度分析，和差示热重分析(TGA/DTA)用于表征。我们的结果表明，通过共沉淀的更高温度和更长的合成时间降低了INDO嵌入的可能性。然而,可以建立16小时的时间和50°C的温度作为插层的最佳条件。体外结果证实了LDH-INDO样品（16小时和50°C）对胃癌（AGP01，ACP02和ACP03）的细胞活力潜力和抗癌活性，乳腺癌（MDA-MB-231和MCF-7），黑色素瘤（SK-MEL-19），肺成纤维细胞（MRC-5），MTT法检测非肿瘤性胃组织(MN01)。细胞增殖受到抑制，证明对MDA-MB-231和SK-MEL-19的毒性较高和较低。因此，建议将INDO的临床重定向作为化疗治疗中不可或缺的辅助抗癌药物。
