Department of Pharmacology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
Sci Rep. 2022 Oct 28;12(1):18148. doi: 10.1038/s41598-022-22562-w.
Available therapeutic strategies for cancers have developed side effects, resistance, and recurrence that cause lower survival rates. Utilizing targeted drug delivery techniques has opened up new hopes for increasing the efficacy of cancer treatment. The current study aimed to investigate the appropriate condition of primming human amniotic epithelial cells (hAECs) with paclitaxel as a dual therapeutic approach consisting of inherent anticancer features of hAECs and loaded paclitaxel. The effects of paclitaxel on the viability of hAECs were evaluated to find an appropriate loading period. The possible mechanism of hAECs paclitaxel resistance was assessed using verapamil. Afterward, the loading and releasing efficacy of primed hAECs were evaluated by HPLC. The anti-neoplastic effects and apoptosis as possible mechanism of conditioned media of paclitaxel-loaded hAECs were assessed on breast and cervical cancer cell lines. hAECs are highly resistant to cytotoxic effects of paclitaxel in 24 h. Evaluating the role of P-glycoproteins in hAECs resistance showed that they do not participate in hAECs resistance. The HPLC demonstrated that hAECs uptake/release paclitaxel with optimum efficacy in 8000 ng/ml treatment. Assessing the anti-proliferative effect of primed hAECs condition media on cancer cells showed that the secretome induced 3.3- and 4.8-times more potent effects on MCF-7 and HeLa, respectively, and enhanced the apoptosis process. These results suggest that hAECs could possibly be used as a drug delivery system for cancer treatment. Besides, inherent anticancer effects of hAECs were preserved during the modification process. Synergistic anticancer effects of paclitaxel and hAECs can be translated into clinical practice, which would be evaluated in the future studies.
现有的癌症治疗策略已经发展出副作用、耐药性和复发，导致生存率降低。利用靶向药物输送技术为提高癌症治疗效果带来了新的希望。本研究旨在探讨紫杉醇对人羊膜上皮细胞（hAECs）进行预培养的合适条件，作为一种包含 hAECs 固有抗癌特性和负载紫杉醇的双重治疗方法。评估紫杉醇对 hAECs 活力的影响，以找到合适的加载期。使用维拉帕米评估 hAECs 紫杉醇耐药的可能机制。随后，通过 HPLC 评估预培养 hAECs 的加载和释放效果。评估载紫杉醇 hAECs 条件培养基的抗肿瘤作用和凋亡作为可能的机制，对乳腺癌和宫颈癌细胞系进行研究。hAECs 在 24 小时内对紫杉醇的细胞毒性作用具有高度耐药性。评估 P-糖蛋白在 hAECs 耐药中的作用表明，它们不参与 hAECs 耐药。HPLC 表明，hAECs 以 8000ng/ml 处理时，摄取/释放紫杉醇的效果最佳。评估预培养 hAECs 条件培养基对癌细胞的抗增殖作用表明，其分泌组对 MCF-7 和 HeLa 的抑制作用分别增强了 3.3 倍和 4.8 倍，并增强了凋亡过程。这些结果表明，hAECs 可能可用作癌症治疗的药物输送系统。此外，hAECs 的固有抗癌作用在修饰过程中得以保留。紫杉醇和 hAECs 的协同抗癌作用可以转化为临床实践，这将在未来的研究中进行评估。
