B7-H7 siRNA与紫杉醇联合治疗胃癌:它们如何改善其疗效?
Cooperative Treatment of Gastric Cancer Using B7-H7 siRNA and Docetaxel; How Could They Modify Their Effectiveness?
发表日期:2023 Jul
作者:
Nadia Bolandi, Mohammad Hassan Khadem Ansari, Yousef Rasmi, Behzad Baradaran
来源:
GENES & DEVELOPMENT
摘要:
尽管胃癌(GC)的患病率很高,但药物耐药是有效化疗的主要问题。B7-H7是B7超家族的新成员,在大多数常见的癌症中都有表达。然而,B7-H7在胃癌侵袭性和化疗敏感性方面的作用仍不清楚。因此,本研究旨在评估使用小干扰RNA(siRNA)抑制B7-H7结合多西他赛对胃癌细胞的影响。应用MTT试验确定多西他赛的IC50和B7-H7 siRNA与多西他赛对MKN-45细胞存活率的联合效应。通过qRT-PCR测定B7-H7、BCL-2、BAX和Caspase-3-8-9基因的表达。此外,应用流式细胞术评价细胞凋亡和细胞周期状态。最后,应用创伤恢复试验和集落形成试验评估该联合治疗对细胞迁移能力和集落形成能力的影响。B7-H7抑制增加了MKN-45细胞对多西他赛的化疗敏感性。在MKN-45胃癌细胞中使用B7-H7 siRNA和多西他赛后,B7-H7 mRNA的表达减少。此外,B7-H7抑制结合多西他赛减少了细胞迁移和集落形成率,阻滞了细胞周期在G2-M期,并通过调节凋亡靶基因的表达诱导凋亡。B7-H7在胃癌的化疗敏感性和发病机制中起到重要作用。因此,B7-H7抑制结合多西他赛可能是治疗胃癌的一种有希望的治疗方法。©2023 作者。
Despite the high prevalence of gastric cancer (GC), drug resistance is a major problem for effective chemotherapy. B7-H7 is a novel member of the B7 superfamily and is expressed in most common cancers. However, the role of B7-H7 on the aggressiveness of GC and chemosensitivity has remained unknown. Therefore, this study was designed to assess the effect of B7-H7 suppression using small interference RNA (siRNA) in combination with docetaxel on GC cells.MTT test was applied to determine the IC50 of docetaxel and the combined effect of B7-H7 siRNA and docetaxel on the viability of the MKN-45 cells. To determine B7-H7, BCL-2, BAX, and caspase-3-8-9 genes expression, qRT-PCR was performed. Furthermore, flow cytometry was applied to evaluate apoptosis and the cell cycle status. Finally, to evaluate the effect of this combination therapy on migratory capacity and colony-forming ability, wound healing assay and colony formation test were employed, respectively.B7-H7 suppression increased the chemo-sensitivity of MKN-45 cells to docetaxel. The expression of B7-H7 mRNA was reduced after using B7-H7 siRNA and docetaxel in MKN-45 GC cells. Also, B7-H7 suppression alongside docetaxel reduced cell migration and colony formation rate, arrested the cell cycle at the G2-M phase, and induced apoptosis by modulating the expression of apoptotic target genes.B7-H7 plays a significant role in the chemo-sensitivity and pathogenesis of GC. Therefore, B7-H7 suppression, in combination with docetaxel, may be a promising therapeutic approach in treating GC.©2023 The Authors.