CAJ | 학술논문

目的：探讨Carfilzomib（ CFZ）联合伊立替康（ CPT?11）对胃癌SGC?7901细胞增殖、凋亡及核因子（ NF）?κB水平的影响。方法采用噻唑蓝比色法检测不同浓度CFZ（0、0?1、1、10、50、100nmol／L）或CPT?11（0、2?5、5、10、50、100μmol／L）及100nmol／L CFZ联合100μmol／L CPT?11处理SGC?7901细胞24、48、72、96h的增殖抑制率，采用流式细胞仪Annexin V／PI双染流式细胞术检测CFZ联合CPT?11处理48h的凋亡率和细胞周期，流式细胞术检测细胞内活化caspase?3的表达，采用Western blotting检测CFZ联合CPT?11处理48h的NF?κB、IκB?α水平及PI3K／Akt信号通路的活化情况。结果 CFZ联合CPT?11或两者单用可呈时间和剂量依赖的方式升高SGC?7901细胞增殖抑制率，且CFZ联合CPT?11的增殖抑制率高于CFZ或CPT?11单用，差异有统计学意义（ P＜0?05）；与CFZ或CPT?11单用相比，CFZ联合CPT?11处理48h的凋亡率、caspase?3活化率、S期细胞比例及IκB?α水平均升高， G2／M 期细胞比例、NF?κB p65及 p?Akt 水平均降低，差异均有统计学意义（ P＜0?05）。结论 CFZ和CPT?11对胃癌SGC?7901细胞均有细胞毒性，如抑制增殖、诱导凋亡、下调NF?κB及抑制PI3K／Akt信号通路活化，CFZ联合CPT?11对胃癌细胞具有协同增效的作用。
목적：탐토Carfilzomib（ CFZ）연합이립체강（ CPT?11）대위암SGC?7901세포증식、조망급핵인자（ NF）?κB수평적영향。방법채용새서람비색법검측불동농도CFZ（0、0?1、1、10、50、100nmol／L）혹CPT?11（0、2?5、5、10、50、100μmol／L）급100nmol／L CFZ연합100μmol／L CPT?11처리SGC?7901세포24、48、72、96h적증식억제솔，채용류식세포의Annexin V／PI쌍염류식세포술검측CFZ연합CPT?11처리48h적조망솔화세포주기，류식세포술검측세포내활화caspase?3적표체，채용Western blotting검측CFZ연합CPT?11처리48h적NF?κB、IκB?α수평급PI3K／Akt신호통로적활화정황。결과 CFZ연합CPT?11혹량자단용가정시간화제량의뢰적방식승고SGC?7901세포증식억제솔，차CFZ연합CPT?11적증식억제솔고우CFZ혹CPT?11단용，차이유통계학의의（ P＜0?05）；여CFZ혹CPT?11단용상비，CFZ연합CPT?11처리48h적조망솔、caspase?3활화솔、S기세포비례급IκB?α수평균승고， G2／M 기세포비례、NF?κB p65급 p?Akt 수평균강저，차이균유통계학의의（ P＜0?05）。결론 CFZ화CPT?11대위암SGC?7901세포균유세포독성，여억제증식、유도조망、하조NF?κB급억제PI3K／Akt신호통로활화，CFZ연합CPT?11대위암세포구유협동증효적작용。
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.