前列腺癌(PC)是全球男性中最常见的恶性肿瘤之一。紫杉醇是广泛用于治疗不同类型癌症的化学治疗剂。最近的研究表明,miRNAs控制着各种基因,这些基因影响着许多生物学和病理过程的调节,例如癌症的形成和发展。化疗耐药,等。
■在三个PC细胞系(PC3,DU-145,LNCAP)之间,PC3显示出最低的miR-145表达并且被选择用于实验。用紫杉醇和miR-145分别或组合处理PC3细胞。为了测量细胞活力,迁徙能力,自噬,细胞周期进程,和凋亡诱导,MTT测定,伤口愈合试验,和膜联蛋白V/PI凋亡试验,分别。此外,采用实时定量PCR(qRT-PCR)检测细胞凋亡相关基因的表达水平,迁移,和干性属性。
■结果表明,miR-145转染可以通过调节相关基因的表达,增强PC3细胞对紫杉醇的敏感性,增加紫杉醇诱导的细胞凋亡。包括Caspase-3,Caspase-9,Bax,Bcl-2此外,结果显示,联合治疗在亚G1期增加了细胞周期停滞.miR-145和紫杉醇协同降低迁移能力和相关转移和干性基因表达,包括MMP-2、MMP-9、CD44和SOX-2。此外,联合治疗可抑制MDR1表达。
■这些结果证实,与单一处理相比,miR-145联合紫杉醇可以抑制细胞增殖和迁移,并增加PC3细胞的化学敏感性。所以,miR-145联合治疗可用作PC治疗的有希望的方法。
UNASSIGNED: Prostate cancer (PC) is one of the most commonly diagnosed malignancies among men worldwide. Paclitaxel is a chemotherapeutic agent widely used to treat different types of cancer. Recent studies revealed miRNAs control various genes that influence the regulation of many biological and pathological processes such as the formation and development of cancer, chemotherapy resistance, etc.
UNASSIGNED: Between three PC cell lines (PC3, DU-145, LNCAP), PC3 showed the lowest miR-145 expression and was chosen for experiments. PC3 cells were treated with paclitaxel and miR-145 separately or in combination. To measure the cell viability, migratory capacity, autophagy, cell cycle progression, and apoptosis induction, the MTT assay, wound-healing assay, and Annexin V/PI apoptosis assay were used, respectively. Moreover, quantitative real-time PCR (qRT-PCR) was employed to measure the expression level of genes involved in apoptosis, migration, and stemness properties.
UNASSIGNED: Obtained results illustrated that miR-145 transfection could enhance the sensitivity of PC3 cells to paclitaxel and increase paclitaxel-induced apoptosis by modulating the expression of related genes, including Caspase-3, Caspase-9, Bax, and Bcl-2. Also, results showed combination therapy increased cell cycle arrest at the sub-G1 phase. miR-145 and paclitaxel cooperatively reduced migration ability and related-metastatic and stemness gene expression, including MMP-2, MMP-9, CD44, and SOX-2. In addition, combination therapy can suppress MDR1 expression.
UNASSIGNED: These results confirmed that miR-145 combined with paclitaxel cooperatively could inhibit cell proliferation and migration and increase the chemosensitivity of PC3 cells compared to mono treatment. So, miR-145 combination therapy may be used as a promising approach for PC treatment.