Department of Pharmacy, The Second Hospital of Dalian Medical University, Dalian, Liaoning 116027, P.R. China.
Mol Med Rep. 2024 Feb;29(2). doi: 10.3892/mmr.2023.13148. Epub 2023 Dec 15.
The objective of the present study was to develop exosomes (EXOs) encapsulating tetramethylpyrazine (TMP) for the reversal of drug resistance in ovarian cancer therapy. Human A2780 cells were incubated with TMP for 48 h. Purified TMP‑primed EXOs (EXOs‑TMP) were isolated through ultracentrifugation. The developed EXOs‑TMP were characterized using techniques such as transmission electron microscopy, nanoparticle tracking analysis, Fluorescence microscopy and western blotting. Subsequently, MTT, western blotting and flow cytometry assays were performed to evaluate the biological effects in drug‑resistant A2780T cells. The results demonstrated that the incorporation of TMP into EXOs exhibited an anti‑ovarian cancer effect and markedly enhanced the antitumor efficacy of paclitaxel (PTX). Furthermore, it was identified that the ability of EXO‑TMP to reverse cell resistance was associated with the downregulation of multidrug resistance protein 1, multidrug resistant‑associated protein 1 and glutathione S‑transferase Pi protein expression. Flow cytometry analysis revealed that EXO‑TMP induced apoptosis in drug‑resistant cells and enhanced the apoptotic effect when combined with PTX. EXOs are naturally sourced, exhibit excellent biocompatibility and enable precise drug delivery to target sites, thereby reducing toxic side effects. Overall, EXO‑TMP exhibited direct targeting capabilities towards A2780T cells and effectively reduced their drug resistance. EXOs‑TMP provide a novel and effective drug delivery pathway for reversing drug resistance in ovarian cancer.
本研究旨在开发载有川芎嗪（TMP）的外泌体（EXOs），以逆转卵巢癌治疗中的耐药性。将人 A2780 细胞与 TMP 孵育 48 h。通过超速离心分离纯化 TMP 预载的 EXOs（EXOs-TMP）。采用透射电子显微镜、纳米颗粒跟踪分析、荧光显微镜和 Western blot 等技术对所开发的 EXOs-TMP 进行表征。随后，通过 MTT、Western blot 和流式细胞术检测评估耐药 A2780T 细胞中的生物学效应。结果表明，TMP 被包裹于 EXOs 中表现出抗卵巢癌作用，并显著增强紫杉醇（PTX）的抗肿瘤疗效。此外，研究发现 EXO-TMP 逆转细胞耐药的能力与多药耐药蛋白 1、多药耐药相关蛋白 1 和谷胱甘肽 S-转移酶 Pi 蛋白表达下调有关。流式细胞术分析显示，EXO-TMP 诱导耐药细胞凋亡，并与 PTX 联合增强凋亡效应。EXOs 具有天然来源、优异的生物相容性，并能精确地将药物递送至靶位，从而减少毒副作用。总体而言，EXO-TMP 对 A2780T 细胞具有直接靶向作用，并有效降低其耐药性。EXO-TMP 为逆转卵巢癌耐药提供了一种新的有效药物递送途径。
