Genetic transfer of PNAS‐4 induces apoptosis and enhances sensitivity to gemcitabine in lung cancer

Abstract

PNAS-4 has been demonstrated to induce apoptosis in U2OS cells. To evaluate its feasibility as a new strategy for cancer therapy, we analyzed its anti-tumor effect with or without gemcitabine in A549 lung cancer cells. MTT assay, Hoechst 33258 staining and flow cytometric analysis were used to determine the cytotoxicity of PNAS-4 alone or plus gemcitabine. The anti-tumor efficacy was further investigated in vivo with nude mice. PNAS-4 plasmid/liposome complexes were injected by tail vein every 4 days. Gemcitabine was given ip on a weekly schedule for 4 weeks. PNAS-4 alone and plus gemcitabine induced apoptosis in A549 cells in vitro. The xenograft lung cancer treated with PNAS-4 retarded growth compared with the empty vector. The combination of PNAS-4 with gemcitabine induced anti-tumor activity accompanied by an increase in apoptotic cells compared with PNAS-4 or gemcitabine alone. No other obvious toxicity was found. PNAS-4 therefore suppresses tumor growth in vivo and enhances sensitivity to gemcitabine. This suggests that the PNAS-4 gene could be a potential candidate for lung cancer therapy alone or in combination with gemcitabine.

PNAS-4, an Early DNA Damage Response Gene, Induces S Phase Arrest and Apoptosis by Activating Checkpoint Kinases in Lung Cancer Cells

“…Lower than That in Adjacent Lung Tissues-Our previous observations have shown that hPNAS-4 overexpression suppresses growth of some lung cancer cells and enhances sensitivity to DNA-damaging agents, including cisplatin, gemcitabine, and radiation in lung cancer cells (10,13,14). However, the majority of the experiments were performed by overexpression of PNAS-4, which may cause artifacts.…”

Identification, Characterization, and Effects ofXenopus laevisPNAS-4 Gene on Embryonic Development

“…In our previous studies, we proved that the overexpression of PNAS-4 induced cancer cell apoptosis via the activation of a mitochondrial pathway [12]. The potential antitumor effects of human PNAS-4 were also demonstrated [13, 14]. To understand the biological function of the PNAS-4 gene in development, we first cloned the homologous PNAS-4 gene from X. laevis based on PNAS-4 bioinformatics analysis.…”

Prokaryotic expression, purification and characterization of a novel pro‐apoptosis protein hPNAS‐4

“…Also, the porcine PNAS‐4 gene has been sequenced, and its expression and its relationship with meat production traits were also analysed [6]. More importantly, we had evaluated the effect of hPNAS‐4 against ovarian cancer [8] and lung cancer [9] in vitro and in nude mice. We found that tumour growth significantly decreased in vivo , and the increased apoptosis of tumour cells as well as decreased angiogenesis in tumour tissue were also observed, which indicated that hPNAS‐4 has potential as a new gene therapy for human cancer.…”

“…We found that tumour growth significantly decreased in vivo , and the increased apoptosis of tumour cells as well as decreased angiogenesis in tumour tissue were also observed, which indicated that hPNAS‐4 has potential as a new gene therapy for human cancer. Furthermore, the combination of hPNAS‐4 and a chemical reagent, gemcitabine, could enhance sensitivity to gemcitabine [9].…”

“…Based on our previous work on PNAS‐4 [4,5,8,9], in the present study we mainly describe the purification, characterization, polyclonal antibody production and subcellular localization of hPNAS‐4 protein. This purified hPNAS‐4 protein and the prepared polyclonal antibodies may provide a powerful tool for the study of the apoptotic mechanisms of hPNAS‐4.…”