Effects of Carfilzomib combined with CPT-11 on the proliferation, apoptosis and NF-kappa B(NF-κB) of gastric cancer SGC-7901 cells

ZHOU Lianghua; WANG Mingyuan; WANG Xing

Abstract：Objective To explore the effects of Carfilzomib ( CFZ) combined with irinotecan ( CPT?11) on the proliferation, apoptosis and NF?kappa B of gastric cancer SGC?7901 cells. Methods The proliferation inhibition rates after treatment with different concentrations of CFZ (0, 0?1, 1, 10, 50,100nmol/L), CPT?11 (0, 2?5, 5, 10, 50, 100μmol/L) or 100nmol/L CFZ plus 100μmol/L CPT?11 were analyzed via MTT colorimetric assay at 24, 48, 72 and 96h. The flow cytometry with Annexin V/PI double staining was used to evaluate the combined effect of CPT?11 and CFZ on apoptosis and cell cycle at 48h, respectively. The intracellular activation of caspase?3 was detected by flow cytometry. Western blotting method was used to measure the protein levels of NF?κB and IκB?α as well as the activation status of PI3K/Akt signaling pathway. Results The co?administration of CFZ and CPT?11 or single?a?gent treatment could increase the proliferation inhibition rates of SGC?7901 cell in a time? and dose?dependent manner, while there were higher proliferation inhibition rate in co?administration versus single?agent treatment ( P<0?05) . Compared with the single?agent treatment, the co?administration of CFZ and CPT?11 presented increasing apoptosis rate, activation rate of caspase?3, proportion of S phase and IκB?αlevel but decreasing proportion of G2/M cell phase, NF?κB p65 and p?Akt level ( P<0?05) . Conclusion Both CFZ and CPT?11 exhibited cytotoxicity on SGC?7901 cell, including proliferative inhibition, induction of apoptosis, downregulation of NF?kappa B and suppression of the activation of PI3K/Akt signaling pathway. CFZ combined with CPT?11 have a synergistic effect on gas?tric cancer cells.