Combined effect of 125 I and gemcitabine on PANC-1 cells: Cellular apoptosis and cell cycle arrest

• Published in: Journal of cancer research and therapeutics Vol. 14; no. 7; p. 1476
• Main Authors: Li, Dong, Jia, Yun-Ming, Cao, Pi-Kun, Wang, Wei, Liu, Bin, Li, Yu-Liang
• Format: Journal Article
• Language: English
• Published: India 2018
• Subjects: Apoptosis - drug effects; Apoptosis - radiation effects; Biomarkers; Cell Cycle Checkpoints - drug effects; Cell Cycle Checkpoints - radiation effects; Cell Line, Tumor; Cell Proliferation - drug effects; Cell Proliferation - radiation effects; Cell Survival - drug effects; Cell Survival - radiation effects; Cells, Cultured; Deoxycytidine - analogs & derivatives; Deoxycytidine - pharmacology; Humans; Iodine Radioisotopes - administration & dosage; Pancreatic Neoplasms - genetics; Pancreatic Neoplasms - metabolism; 125I; pancreatic cancer; gemcitabine
• ISSN: 0973-1482; 1998-4138
• DOI: 10.4103/jcrt.JCRT_43_18

I seed implantation has recently become an effective, safe, and feasible treatment for advanced pancreatic cancer in China. Gemcitabine (GEM), superior to fluorouracil, has been widely proved as effective chemotherapy for many solid tumors and become the standard treatment for locally advanced and metastatic pancreatic cancer. The study aimed to evaluate the combined effect of I and GEM on pancreatic carcinoma cells (PANC-1) cells and explore the underlying molecular basis. PANC-1 cells were treated with I continuously at a low dose of radiation, combined with or without sensitizing concentration of GEM. The clonogenic capacity, cellular proliferation, cell cycle distribution, apoptosis, and molecular pathways of the cells following these treatments were analyzed in vitro. The cell growth could be significantly inhibited after the treatment with GEM or I alone, while the inhibition effects would be greater with combination therapy than either monotherapy (72 h, C vs. GEM, t = 16.59, P < 0.01; C vs. I, t = 9.808, P < 0.05; C vs. I + GEM, t = 17.87, P < 0.01; I vs. I+GEM, t = 8.191, P < 0.05). GEM increased radiation-induced apoptosis (4 Gy, I vs. I+GEM, t = 10.43, P < 0.01) and induced the arrest of G1. Caspase-3 expression and the Bax/Bcl2 ratio were lower in cells receiving combination treatment than that of in cells treated with I or GEM alone. The combined treatment of I and GEM-induced stronger anti-proliferation effect than single-treatment, due to the cell cycle arrest and more cellular apoptosis in PANC-1 cells. The increased Bax/Bcl-2 ratio may lead to enhanced apoptosis.