CAJ | 학술논문

目的：探讨盐酸埃克替尼联合化疗药（多西他赛、培美曲塞）以不同次序序贯及选择合理用药时机用药对非小细胞肺癌细胞系GLC-82的作用。方法：运用xCELLigence系统检测多西他赛、培美曲塞、盐酸埃克替尼单药作用GLC-82的IC50，及单药在GLC-82细胞内的时间依赖性IC50，并检测盐酸埃克替尼不同次序联合多西他赛、培美曲塞对GLC-82的增殖毒性，用流式细胞仪检测埃克替尼与二者联合的不同次序对GLC-82细胞的细胞周期影响。结果：多西他赛、培美曲塞在作用36 h后在细胞内达到平衡期，而埃克替尼在作用60 h后在细胞内达到平衡期。多西他赛作用于GLC-82细胞系36 h的IC50为25 mg·mL-1，培美曲塞作用于GLC-82细胞系36 h的IC50为560μmol·L-1，埃克替尼作用于GLC-82细胞系60 h的IC50为10μmo·L-1。先用多西他赛或培美曲塞后用埃克替尼方案与其他用药方案相比，细胞倍增时间显著增加：D-I组倍增时间为（–829.1±46.9） h；P-I组倍增时间为（–342.0±3.4） h，与其他序贯联合方式相比，差异有统计学意义（P <0.05）；并可使细胞阻滞在G2/M期（培美曲塞阻滞在S期），细胞生长抑制效果更好（P <0.05）。结论：先于埃克替尼使用多西他赛或培美曲塞，并且选择合理的用药时机为体外抑制NSCLC细胞增殖的最佳联用方案。
목적：탐토염산애극체니연합화료약（다서타새、배미곡새）이불동차서서관급선택합리용약시궤용약대비소세포폐암세포계GLC-82적작용。방법：운용xCELLigence계통검측다서타새、배미곡새、염산애극체니단약작용GLC-82적IC50，급단약재GLC-82세포내적시간의뢰성IC50，병검측염산애극체니불동차서연합다서타새、배미곡새대GLC-82적증식독성，용류식세포의검측애극체니여이자연합적불동차서대GLC-82세포적세포주기영향。결과：다서타새、배미곡새재작용36 h후재세포내체도평형기，이애극체니재작용60 h후재세포내체도평형기。다서타새작용우GLC-82세포계36 h적IC50위25 mg·mL-1，배미곡새작용우GLC-82세포계36 h적IC50위560μmol·L-1，애극체니작용우GLC-82세포계60 h적IC50위10μmo·L-1。선용다서타새혹배미곡새후용애극체니방안여기타용약방안상비，세포배증시간현저증가：D-I조배증시간위（–829.1±46.9） h；P-I조배증시간위（–342.0±3.4） h，여기타서관연합방식상비，차이유통계학의의（P <0.05）；병가사세포조체재G2/M기（배미곡새조체재S기），세포생장억제효과경호（P <0.05）。결론：선우애극체니사용다서타새혹배미곡새，병차선택합리적용약시궤위체외억제NSCLC세포증식적최가련용방안。
Objective: To investigate the effects of icotinib combined with chemotherapy drugs (docetaxel or pemetrexed) in different sequential therapies and therapy timings on non-small-cell lung cancer cell line GLC-82.Methods:The IC50 of docetaxel, pemetrexed and icotinib on GLC-82 and time dependence of each agent were analyzed by xCELLigence system. The proliferations of GLC-82 were compared in different sequential therapies of icotinib combined with docetaxel or pemetrexed. Cell cycle distribution of GLC-82 was measured by lfow cytometer for evaluating different sequential therapies, and the cell survival was analyzed by xCELLigence system.Results:At the time of 36 h, docetaxel and pemetrexed reached their balance periods in cells, while icotinib reached its balance period at the time of 60 h. The IC50 of docetaxel and pemetrexed on GLC-82 cell line for 36 hours were 25 mg·mL-1 and 560 μmol·L-1, respectively; the IC50 of icotinib on GLC-82 cell line for 60 hours was 10 μmol·L-1. Compared with the other groups, the doubling time of GLC-82 increased signiifcantly in sequential administration of docetaxel or pemetrexed followed by icotinib groups (P< 0.05). The doubling times of GLC-82 in the D-I group and P-I group were (–829.1 ± 46.9) h and (–342.0 ± 3.4) h, respectively. D-I group induced G2/M phase arrest and P-I group induced S phase arrest. These two kinds of administrations had better inhibiting effects on cell growth (P < 0.05).Conclusion:Sequential administration of docetaxel or pemetrexed followed by icotinib at a reasonable time is the optimal combination schedule for the antiproliferative effects of NSCLC cellsin vitro.