DADS对TE-1体外以及裸鼠体内生长的影响及作用机制

目的探讨二烯丙基二硫化物（DADS）对TE-1细胞体外以及裸鼠体内生长的影响及其作用机制。方法MTT法检测24h、48h不同浓度DADS体外对食管癌TE—1细胞活力的影响。使用TE-1细胞建立裸鼠皮下移植瘤模型，分为对照组和DADS低浓度治疗组（20mg／kg）、DADS高浓度治疗组（40mg／kg），腹腔注射14次，隔日1次，观察动物状态并监测移植瘤生长状况，28d后处死动物，使用Western blot检测不同组别移植瘤中磷酸化p38、磷酸化ERKI／2、caspase-3、活化caspase-3的表达水平。结果MTT、结果提示DADS能够在体外抑制TE-1的增殖，且具有剂量依赖性。DADS药物治疗组移植瘤生长速度明显低于对照组，以高剂量组为著。Western blot检测结果显示，DADS药物组移植瘤中p38MAPK磷酸化水平升高、ERK1／2的磷酸化水平显著降低，活化caspase-3水平明显升高，且均呈剂量依赖性（P〈0．05）。结论DADS在裸鼠体外、体内均能显著抑制人食管癌TE-1细胞的生长，其作用机制可能与DADS活化p38MAPK通路并抑制ERK通路，活化caspase-3进而抑制肿瘤增殖并促进TE-1细胞凋亡有关。

Influence of DADS on the growth of esophageal cancer cells TE-1 in vitro and in vivo in nude mice and its mechanism

Objective To investigate the influence of DADS on the growth of esophageal cancer cells TE-1 in vitro and in vivo and its mechanism. Methods MTT assay was used to determine the inhibitory effects of DADS on TE-1 cells in vitro at 24,48 h. TE-1 cells were used to establish the esophageal cancer xenograft models in nude mice, and then were randomly divided into control group, DADS low concentration group, and DADS high concentration group. The mice were intraperitoneally injected with 20 mg/kg and 40 mg/kg DADS 14 times every other day in DADS groups,respectively. The tumor size and status of mice were observed every other day. Ani-mals were sacrificed at 28 d. Western blot was employed to detect the levels of p-p38MAPK,p-ERK1/2, caspase-3 and activated caspase-3 in xenograft tissues. Results MTT assay showed that DADS inhibited TE-1 cells proliferation in vitro in a dose-dependent manner. Tumor growth in DADS groups, especially in high concentration DADS group,was significantly slower than that in control group （P 〈0.05）. Western blot test showed that the p-p38MAPK and activated caspase-3 proteins expression in xenografts significantly in- creased in DADS groups in comparison with control group,and p-ERK1/2 levels were significantly decreased in a dose-dependent man- ner （P 〈 0.05 ）. Conclusion DADS can significantly inhibit TE-1 cell proliferation in vitro and in vivo, which may be caused by the activation of caspase-3 and p38MAPK pathway and the suppression of ERK signaling pathway.