Key Laboratory of Biotechnology for Medicinal Plants of Jiangsu Province, Xuzhou Normal University, 101 Shanghai Road, Xuzhou, China.
Biomed Pharmacother. 2012 Apr;66(3):187-94. doi: 10.1016/j.biopha.2011.10.007. Epub 2012 Jan 18.
Multidrug resistance (MDR) is a major barrier for chemotherapy of many cancers. Non-ionic surfactants have great potential to reverse the MDR by preventing onset or delay progression of the carcinogenic process. However, the role of Tween-20 in the development of MDR remains unknown. The aim of this study was to explore the reversal effect and potential mechanism of Tween-20 on tumor cells in vitro. Alamar Blue assay was used to examine the reversal index of Tween-20 to vincristine (VCR), doxorubicin (DOX) and 5-fluorouracil (5-FU) in KBv200, HepG2/R and Bel-7402/5-FU, respectively. Morphological change was determined by Gimsa and Hoechst 33258 staining. The acumulation of DOX was confirmed by spectrofluorimetric assay. Cell cycle analysis was performed using flow cytometry. The mRNA and protein expression levels of MDR were assessed by semiquantitative RT-PCR and dot blot, respectively. The results showed that Tween-20 at concentrations of 0.0025%, 0.005%, 0.01% had little cytotoxicity. When combined with the cancer drugs, it significantly promoted the sensitivity of MDR cells. Fluorescence staining confirmed that the percentage of apoptotic cell increased when combined with Tween-20. This notion was further supported by the observation that Tween-20 treatment potentiated VIN-induced G2/M arrest of the cell cycle. Furthermore, Tween-20 treatment increased significantly intracellular accumulation of DOX. RT-PCR and dot blot revealed that Tween-20 could downregulate the expression of MDR and P-glycoprotein. Low concentrations of Tween-20 can efficiently reverse the multidrug resistance phenotype by enhancing accumulation of the anticancer drugs. The potential mechanism may be via inhibiting the multidrug-resistant gene expression.
多药耐药（MDR）是许多癌症化疗的主要障碍。非离子型表面活性剂通过防止致癌过程的发生或延缓其进展，具有逆转 MDR 的巨大潜力。然而，Tween-20 在 MDR 发展中的作用尚不清楚。本研究旨在探讨 Tween-20 在体外对肿瘤细胞的逆转作用及其潜在机制。使用 Alamar Blue 法检测 Tween-20 对 KBv200、HepG2/R 和 Bel-7402/5-FU 细胞中长春新碱（VCR）、阿霉素（DOX）和 5-氟尿嘧啶（5-FU）的逆转指数。吉姆萨和 Hoechst 33258 染色观察形态学变化。荧光分光光度法检测 DOX 的蓄积。流式细胞术检测细胞周期。半定量 RT-PCR 和斑点印迹法检测 MDR 的 mRNA 和蛋白表达水平。结果表明，浓度为 0.0025%、0.005%和 0.01%的 Tween-20 对细胞的毒性较小。与抗癌药物联合使用时，能显著提高 MDR 细胞的敏感性。荧光染色证实，与 Tween-20 联合使用时，凋亡细胞的比例增加。这一观点得到了进一步的支持，即 Tween-20 处理增强了 VIN 诱导的细胞周期 G2/M 期阻滞。此外，Tween-20 处理显著增加了 DOX 的细胞内蓄积。RT-PCR 和斑点印迹法显示，Tween-20 能下调 MDR 和 P-糖蛋白的表达。低浓度的 Tween-20 可通过增强抗癌药物的蓄积，有效地逆转多药耐药表型。其潜在机制可能是通过抑制多药耐药基因的表达。
