Khazaei Mozafar, Pazhouhi Mona, Khazaei Saber
Fertility and Infertility Research Center, Health Technology Institute, Kermanshah University of Medical Sciences, Kermanshah, Iran.
Department of Endodontics, Dental Research Center, Isfahan University of Medical Sciences, Isfahan, Iran.
Med J Islam Repub Iran. 2019 May 6;33:39. doi: 10.34171/mjiri.33.39. eCollection 2019.
Glioblastoma multiforme (GBM) is the most malignant primary brain tumor. Temozolomide (TMZ) is a chemotherapeutic agent that has been used in GBM treatment. Resistance to TMZ is a major obstacle to successful GBM treatment. The aim of the present study was to investigate the effect of TMZ and tranilast on human GBM cell line (U87MG). In this in vitro experimental study, the effect of TMZ and tranilast on cell proliferation was measured using the MTT assay. Median effect analysis was performed to determine the TMZ and tranilast interaction. Lactate dehydrogenase assay was used to determine TMZ and tranilast cytotoxicity. Cell fluorescent staining and real-time PCR were used for apoptosis evaluation. The effect of TMZ and tranilast on U87MG nitric oxide (NO) production was evaluated by Griess assay. TMZ and tranilast had a significant dose- and time-dependent inhibitory effect on cell proliferation. The mean combination index values represented a synergistic effect, and dose reduction index values suggested the advantages of reducing the toxicity, adverse effects, and drug resistance in combination of TMZ and tranilast. Apoptosis cell death was induced by TMZ and/or tranilast in cells. TMZ and tranilast reduced NO. production in cells. TMZ and tranilast combination inhibited the GBM cells growth effectively.
多形性胶质母细胞瘤（GBM）是最恶性的原发性脑肿瘤。替莫唑胺（TMZ）是一种用于GBM治疗的化疗药物。对TMZ耐药是GBM治疗成功的主要障碍。本研究的目的是探讨TMZ和曲尼司特对人GBM细胞系（U87MG）的影响。在这项体外实验研究中，使用MTT法测定TMZ和曲尼司特对细胞增殖的影响。进行中位效应分析以确定TMZ和曲尼司特的相互作用。使用乳酸脱氢酶测定法确定TMZ和曲尼司特的细胞毒性。细胞荧光染色和实时PCR用于评估细胞凋亡。通过Griess法评估TMZ和曲尼司特对U87MG一氧化氮（NO）产生的影响。TMZ和曲尼司特对细胞增殖具有显著的剂量和时间依赖性抑制作用。平均联合指数值代表协同效应，剂量降低指数值表明TMZ和曲尼司特联合使用在降低毒性、不良反应和耐药性方面的优势。TMZ和/或曲尼司特诱导细胞凋亡。TMZ和曲尼司特降低细胞中NO的产生。TMZ和曲尼司特联合使用可有效抑制GBM细胞生长。
