The association of changes in RAD51 and survivin expression levels with the proton beam sensitivity of Capan‑1 and Panc‑1 human pancreatic cancer cells

Abstract

Fewer than 20% of patients diagnosed with pancreatic cancer can be treated with surgical resection. The effects of proton beam irradiation were evaluated on the cell viabilities in Panc-1 and Capan-1 pancreatic cancer cells. The cells were irradiated with proton beams at the center of Bragg peaks with a 6-cm width using a proton accelerator. Cell proliferation was assessed with the MTT assay, gene expression was analyzed with semi-quantitative or quantitative reverse transcription-polymerase chain reaction analyses and protein expression was evaluated by western blotting. The results demonstrated that Capan-1 cells had lower cell viability than Panc-1 cells at 72 h after proton beam irradiation. Furthermore, the cleaved poly (ADP-ribose) polymerase protein level was increased by irradiation in Capan-1 cells, but not in Panc-1 cells. Additionally, it was determined that histone H2AX phosphorylation in the two cell lines was increased by irradiation. Although a 16 Gy proton beam was only slightly up-regulated cyclin-dependent kinase inhibitor 1 (p21) protein expression in Capan-1 cells, p21 expression levels in Capan-1 and Panc-1 cells were significantly increased at 72 h after irradiation. Furthermore, it was observed that the expression of DNA repair protein RAD51 homolog 1 (RAD51), a homogenous repair enzyme, was decreased in what appeared to be a dose-dependent manner by irradiation in Capan-1 cells. Contrastingly, the transcription of survivin in Panc-1 was significantly enhanced. The results suggest that RAD51 and survivin are potent markers that determine the therapeutic efficacy of proton beam therapy in patients with pancreatic cancer.

Therapeutic Efficacy of Variable Biological Effectiveness of Proton Therapy in U-CH2 and MUG-Chor1 Human Chordoma Cell Death

“…We also observed downregulation of RAD51B at E-SOBP which is responsible for homologous recombination. We envisaged that E-SOBP might be causing severe DNA damage which could lead to irreparable DNA damage and cell death [ 26 ]. The Ingenuity Pathway Analysis of the gene expression data at both M-SOBP and E-SOBP have shown downregulation of OX40 ligand in OX40 pathway.…”

Arctigenin Enhances the Cytotoxic Effect of Doxorubicin in MDA-MB-231 Breast Cancer Cells

“…H2A.X phosphorylation is the result of DNA damage [32,33], and thus, we speculated that increased DOX-induced H2A.X phosphorylation by ATG reflects an increase in DNA, and that this enhanced MDA-MB-231 cell death ( Figure 1C). Cell death by DNA damage is primarily caused by a failure to repair DNA [34,35], and survivin and RAD51 play important roles in DNA repair [36,37]. Hence, the ATG/DOX-induced suppressions of survivin and RAD51 protein levels suggests increased cell death was due to an inability to repair DNA.…”

Charged Particle Irradiation for Pancreatic Cancer: A Systematic Review of In Vitro Studies

“…The characteristics of included (13)(14)(15)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27)(28)(29)(30)(31)(32)(33)(34) studies are summarized in Table 1. Briefly, 13 carbon ion irradiation and seven proton irradiation studies were included in our final SR; these studies were published between 2004 and 2021.They were conducted in 7 different countries: Japan, Germany, Belgium, Italy, Korea, the United States of America, and Lithuania.…”