Brcc2 gene inhibits lung cancer cell proliferation and invasiveness in vitro and in vivo:prospect for gene therapy

Marziyeh Alizadeh zarei,1,* Elahe seyed hosseini ,2 Hamed haddad kashani ,3 Hossein nikzad,4

1. Anatomical Sciences Research Center, Kashan University of Medical Sciences, Kashan, Iran
2. Anatomical Sciences Research Center, Kashan University of Medical Sciences, Kashan, Iran
3. Anatomical Sciences Research Center, Kashan University of Medical Sciences, Kashan, Iran
4. Anatomical Sciences Research Center, Kashan University of Medical Sciences, Kashan, Iran

Abstract

Introduction

Lung cancer is one of the major causes of cancer related death worldwide .despite recent improvements, resistance to conventional treatments is a major limitation. so development of novel approaches is a clinical priority. to this end, gene therapy has emerged as a promising alternative. brcc2 -an apoptotic member of the bcl-2 family- have been recently found to be downregulated in many human cancers and its downregulation is proved to be associated with tumor progression. so, the aim of the present study was to investigate the role of brcc2 in tumor suppression in lung cancer cells.

Methods

Brcc2 expression level was measured in normal and cancerous lung cells. lung cancer cells proliferation was evaluated by mtt assay. migration and invasion was tested via 24-well transwell assay. moreover, apoptosis induction was analyzed using annexin v/pi kit. furthermore, the effect of brcc2 overexpression on mmp2 and mmp9 expression was assayed by real-time pcr. we also investigated the effect of brcc2 overexpression on tumor formation inhibition in mouse model.

Results

We found that brcc2 expression was significantly downregulated in cancer cells compared with lung normal cells. our results also revealed that brcc2 inhibited cell growth, migration and invasion and metastasis and induced apoptosis in lung cancer cells. an in vivo assay showed that brcc2 dramatically inhibited lung cancer cell xenograft formation.

Conclusion

Our study provided evidence that brcc2 functions as a novel tumor suppressor gene in lung cancer cells and may be a potential therapeutic target for lung cancer management.

Keywords

Brcc2, lung cancer, gene therapy