使用B7-H7小干扰RNA与多西他赛联合治疗胃癌;它们如何改变其疗效?

Cooperative Treatment of Gastric Cancer Using B7-H7 siRNA and Docetaxel; How Could They Modify Their Effectiveness?

作者信息

Bolandi Nadia, Khadem Ansari Mohammad Hassan, Rasmi Yousef, Baradaran Behzad

机构信息

Department of Biochemistry, Faculty of Medicine, Urmia University of Medical Sciences, Urmia, Iran.

Cellular and Molecular Research Center, Urmia University of Medical Sciences, Urmia, Iran.

出版信息

Adv Pharm Bull. 2023 Jul;13(3):573-582. doi: 10.34172/apb.2023.055. Epub 2022 Jul 2.

Abstract

PURPOSE

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.

METHODS

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.

RESULTS

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.

CONCLUSION

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.

摘要

目的

尽管胃癌(GC)的发病率很高,但耐药性是有效化疗的一个主要问题。B7-H7是B7超家族的一个新成员,在大多数常见癌症中都有表达。然而,B7-H7在GC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并联合多西他赛对GC细胞的影响。

方法

应用MTT试验确定多西他赛的IC50以及B7-H7 siRNA与多西他赛联合对MKN-45细胞活力的影响。为了确定B7-H7、BCL-2、BAX和caspase-3-8-9基因的表达,进行了qRT-PCR。此外,应用流式细胞术评估细胞凋亡和细胞周期状态。最后,分别采用伤口愈合试验和集落形成试验评估这种联合治疗对迁移能力和集落形成能力的影响。

结果

抑制B7-H7可增加MKN-45细胞对多西他赛的化疗敏感性。在MKN-45 GC细胞中使用B7-H7 siRNA和多西他赛后,B7-H7 mRNA的表达降低。此外,与多西他赛一起抑制B7-H7可降低细胞迁移和集落形成率,使细胞周期停滞在G2-M期,并通过调节凋亡靶基因的表达诱导细胞凋亡。

结论

B7-H7在GC的化疗敏感性和发病机制中起重要作用。因此,抑制B7-H7联合多西他赛可能是治疗GC的一种有前景的治疗方法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6469/10460818/a18be07a87e8/apb-13-573-g001.jpg

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