Noxa and Puma genes regulated by hTERT promoter can mitigate growth and induce apoptosis in hepatocellular carcinoma mouse model.

ABSTRACT

With significant high incidence and death rates, liver cancer has become one of the most common cancers all over the world. Hence, novel strategies are needed for the management of this malignancy. Apoptotic related proteins Noxa and Puma are the members of BH3-only family. In this study, human Noxa or Puma coding sequences have been inserted into plasmid pcDNA 3.1 regulated by human TERT promoter. The transfection of HepG2 cells with pcTERT-Noxa or pcTET-Puma resulted in the significant suppression of cell proliferation as well as finally led to apoptosis via mitochondrial and death receptor pathways, and also exhibited significantly reduced the ability of invasion and metastasis. Moreover, an in vivo study revealed that intratumoral injections of pcTERT-Noxa or pcTERT-Puma plasmids effectively suppressed the tumor growth and can exhibit anti-neoplastic effects by recruiting CD3, CD8, CD45 positive T lymphocytes in the tumor tissues. Overall, our findings illustrated that pcTERT-Noxa and pcTERT-Puma may exhibit significant anti-tumor effects both in vivo and in vivo.