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

BACKGROUND

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.

SUBJECTS AND METHODS

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.

RESULTS

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.

CONCLUSION

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.