研究动态
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TPGS对肿瘤细胞的抑制作用及其与化疗药物的联合应用的探索。

Exploration of the inhibition action of TPGS on tumor cells and its combined use with chemotherapy drugs.

发表日期:2023 Dec
作者: Lan Tang, Kaijuan Huang, Wenhui Jiang, Lulu Fu, Ran Zhang, Liting Shen, Zhimin Ou, Ye Huang, Zhenhai Zhang
来源: DRUG DELIVERY

摘要:

D-alpha-tocopheryl polyethylene glycol 1000 succinate(TPGS)是一种常用的非离子界面活性剂,用于不同药物传递系统中的制药载体。TPGS可以逆转P-糖蛋白(P-gp)介导的多药耐药(MDR),并具有抗癌活性。这意味着,在设计抗肿瘤药物制剂时,需要考虑TPGS的抗肿瘤活性。我们的体内研究表明,与其他七种肿瘤细胞系相比,TPGS在MCF-7-ADR细胞中表现出最强的细胞毒性。进一步的研究发现,TPGS引起细胞凋亡,并阻止MCF-7细胞在G2 / M期生长。机制研究表明,TPGS增加了细胞内钙离子浓度,通过线粒体途径引起细胞凋亡。此外,进行了两项体内实验。一种是通过尾静脉注射TPGS,DOX溶液治疗裸鼠携带的MCF-7-ADR肿瘤。另一种是通过肿瘤内注射温敏TPGS凝胶(TPGS-TG)和通过尾静脉注射纳米紫杉醇(Abraxane®)结合治疗裸鼠携带的MCF-7-ADR肿瘤。研究结果证实,TPGS可发挥抗肿瘤作用,降低化疗药物的毒性,提高药物耐药性肿瘤的治疗效率,从而提高安全肿瘤治疗的发展。
D-alpha-tocopheryl polyethylene glycol 1000 succinate (TPGS) is a commonly used nonionic surfactant used as a pharmaceutical carrier in different drug delivery systems. TPGS can reverse P-glycoprotein (P-gp)-mediated multidrug resistance (MDR) and also has anticancer activities. It suggests that when designing antitumor drug preparation, it's necessary to take into account the antitumor activity of TPGS. Our in vivo studies showed that TPGS exerted the strongest cytotoxicity in MCF-7-ADR cells when compared with seven other tumor cell lines. The further study revealed TPGS caused apoptosis and blocked MCF-7 cell growth in G2/M phase. Mechanistic insights suggested that TPGS increased intracellular calcium ion concentrations, leading to apoptosis via the mitochondrial pathway. Furthermore, two in vivo experiments were performed. One was TPGS, and DOX solution was administered by tail vein injection on MCF-7-ADR tumor bearing nude mice. The other was temperature sensitive TPGS gel (TPGS-TG) was administered by intratumoral injection on MCF-7-ADR tumor bearing nude mice combined with paclitaxel albumin nanoparticles (Abraxane®) administered by tail vein injection. The findings confirmed that TPGS could play its role in anti-tumor to reduce the toxicity of chemotherapeutic drugs and improve the efficiency of drug-resistant tumors, thereby enhancing the development of safe oncology therapeutics.