Li Xiu-Ying, Li Zhi, An Gui-Jie, Liu Sha, Lai Yan-Dong
Institute of Genomic Medicine, College of Pharmacy, Jinan University 601 Huangpudadao Xi Road, Guangzhou 510632, China.
Institute for Chemical Carcinogenesis, Guangzhou Medical University 195 Dongfeng Xi Road, Guangzhou 510182, China.
Int J Clin Exp Pathol. 2014 Feb 15;7(3):978-86. eCollection 2014.
Granzyme B and perforin, two of the most important components, have shown anticancer properties in various cancers, but their effects in laryngeal cancer remain unexplored. Here we decided to examine the effects of Granzyme B and perforin in Hep-2 cells and clarify the role of perforin and granzyme B in the tumorigenicity of laryngeal cancer cell line. Hep-2 cells were transfected with pVAX1-PIG co-expression vector (comprising perforin and granzyme B genes), and then the growth and apoptosis of these Hep-2 cells were evaluated. The tumorigenicity of Hep-2 cell line co-expressing perforin and granzyme B genes was tested in BALB/c nu/nu mice. We found that the co-expression of perforin and granzyme B genes could obviously inhibit cell focus formation and induce cell apoptosis in Hep-2 cells. Furthermore, after subcutaneous injection of Hep-2 cells transfected with pVAX1-PIG, an extensive delay in tumor growth was observed in BALB/c-nu/nu mice. Moreover, our studies demonstrated that the anticancer activity of perforin and granzyme B was sustainable in vivo as tumor development by inducing cell apoptosis. Taken together, our data indicate that the co-expression of perforin and granzyme B genes exhibits anticancer potential, and hopefully provide potential therapeutic applications in laryngeal cancer.
颗粒酶B和穿孔素是两个最重要的成分,已在多种癌症中显示出抗癌特性,但它们在喉癌中的作用仍未得到探索。在此,我们决定研究颗粒酶B和穿孔素对Hep-2细胞的影响,并阐明穿孔素和颗粒酶B在喉癌细胞系致瘤性中的作用。用pVAX1-PIG共表达载体(包含穿孔素和颗粒酶B基因)转染Hep-2细胞,然后评估这些Hep-2细胞的生长和凋亡情况。在BALB/c nu/nu小鼠中测试共表达穿孔素和颗粒酶B基因的Hep-2细胞系的致瘤性。我们发现,穿孔素和颗粒酶B基因的共表达可明显抑制Hep-2细胞中的细胞集落形成并诱导细胞凋亡。此外,在皮下注射用pVAX1-PIG转染的Hep-2细胞后,在BALB/c-nu/nu小鼠中观察到肿瘤生长出现广泛延迟。而且,我们的研究表明,穿孔素和颗粒酶B的抗癌活性在体内通过诱导细胞凋亡抑制肿瘤发展方面具有持续性。综上所述,我们的数据表明,穿孔素和颗粒酶B基因的共表达具有抗癌潜力,并有望为喉癌提供潜在的治疗应用。