Hosseini Sare, Chamani Jamshidkhan, Sinichi Mohadeseh, Bonakdar Amir Mohammad, Azad Zeinolabedin, Ahangari Najmeh, Rahimi Hamid Reza
Cancer Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.
Department of Biology, Faculty of Sciences, Islamic Azad University-Mashhad Branch, Mashhad, Iran.
Iran J Basic Med Sci. 2019 Oct;22(10):1198-1202. doi: 10.22038/ijbms.2019.35808.8530.
Hepatocellular carcinoma (HCC) is one of the most significant health condition around the world. As the only curative therapies, liver transplantation and surgical resection are the clinical treatments of HCC. Due to the systemic toxicity and severe side effects of these treatments, it is vital to establish new therapeutic approaches. The present study aimed to compare cyclin D1 (CCN D1) gene expression in hepatocellular carcinoma cell line (HUH7) when it is treated with nanomicelle curcumin and sorafenib. The purpose was to identify toxicity risk and antioxidant activity of these drugs.
The toxic dose (IC) of nanomicelle curcumin and sorafenib were detected after treatment of HUH7 cell lines with different dose of mentioned agents followed by MTT assay. CCN D1 gene expression was evaluated using real-time PCR. Following the Tukey's multiple comparison tests, statistical analysis is done through Student's t-test or ANOVA.
The expression of the CCN D1 gene was statistically significant (<0.001) at 289.31, 128 and 152.36 for sorafenib, nanomicelle curcumin and SNC (sorafenib-nanomicelle curcumin) respectively. The finding of this study revealed that, in comparison to sorafenib alone, the treatment of HUH7 with a nanomicelle curcumin IC dose, in combination with sorafenib, might down-regulate CCN D1 gene expression.
The present research indicates that the treatment of the cell line with only nanomicelle curcumin results in the down-regulation of cyclin D1. To further decrease cyclin D1 expression, the co-delivery of curcumin and sorafenib appears to induce the apoptotic process. As a result, the effect of sorafenib cytotoxicity and CCN D1 gene expression decreases twofold.
肝细胞癌(HCC)是全球最重要的健康问题之一。肝移植和手术切除作为仅有的根治性疗法,是HCC的临床治疗手段。由于这些治疗方法存在全身毒性和严重副作用,因此建立新的治疗方法至关重要。本研究旨在比较纳米胶束姜黄素和索拉非尼处理肝细胞癌细胞系(HUH7)时细胞周期蛋白D1(CCN D1)基因的表达情况。目的是确定这些药物的毒性风险和抗氧化活性。
用不同剂量的纳米胶束姜黄素和索拉非尼处理HUH7细胞系后,通过MTT法检测其毒性剂量(IC)。使用实时PCR评估CCN D1基因表达。在进行Tukey多重比较检验后,通过学生t检验或方差分析进行统计分析。
索拉非尼、纳米胶束姜黄素和SNC(索拉非尼 - 纳米胶束姜黄素)处理时,CCN D1基因表达在289.31、128和152.36时具有统计学意义(<0.001)。本研究结果表明,与单独使用索拉非尼相比,用纳米胶束姜黄素IC剂量联合索拉非尼处理HUH7可能会下调CCN D1基因表达。
本研究表明,仅用纳米胶束姜黄素处理细胞系会导致细胞周期蛋白D1下调。为进一步降低细胞周期蛋白D1表达,姜黄素和索拉非尼的共同递送似乎会诱导凋亡过程。因此,索拉非尼细胞毒性和CCN D1基因表达的作用降低了两倍。