多肽P110增强顺铂对结肠癌HCT-116细胞增殖和小鼠移植瘤生长的抑制作用

Polypeptide Pl10 enhances the growth-inhibitory effect of cisplatin on colon cancer HCT-116 cells and xenotransplanted tumors in mice

目的观察针对G3BPs蛋白靶标所设计的多肽P110联合顺铂对人结肠癌HCT-116细胞增殖和小鼠结肠癌C26移植瘤生长的抑制作用。方法采用四甲基偶氮唑蓝（MTT）法检测20μmol／LP110联合不同浓度顺铂对HCT-116细胞和人脐静脉内皮细胞（HUVEC）的增殖抑制作用。建立小鼠结肠癌C26皮下移植瘤模型，观察不同剂量P110和顺铂对小鼠移植瘤的抑制作用。结果20μmol／LP110＋10μmol／L顺铂、20μmol／LP110＋30μmol／L顺铂和20μmol／LP110＋90μmol／L顺铂对HCT-116细胞的增殖抑制率分别为（43．3±3．2）％、（46．4±4．6）％和（47．6±5．8）％，10、30和90μmol／L顺铂对HCT-116细胞的增殖抑制率分别为（15．6±3．3）％、（21．3±1．1）％和（36．0±0．9）％，P110能够增强顺铂对HCT-116细胞增殖的抑制作用，差异均有统计学意义（均P〈0．05）。20μmol／LP110联合10μmol／L顺铂可有效的杀伤HCT-116细胞，且对HUVEC细胞的毒性作用较小。25mg／kgP110＋1mg／kd顷铂、50mg／kgP110＋1mg／kg顺铂、100mg／kgP110＋1mg／kg顺铂对小鼠移植瘤的抑瘤率分别为23．0％、30．4％和34．2％，均高于1mg／kg顺铂的抑瘤率（22．7％）。结论P110能够增强顺铂对结肠癌HCT-116细胞增殖和小鼠结肠癌C26移植瘤生长的抑制作用；联合用药能减少顺铂有效使用剂量，进而减少顺铂的毒性作用。

Objective To observe the growth-inhibitory effect of polypeptide PII0, designed with G3BP protein targets, plus cisplatin on human colon cancer HCT-116 cells and mouse colon cancer C26 xenotransplanted tumors in mice. Methods The proliferation inhibition of HCT-116 cells and HUVEC cells in vitro was evaluated by MTT assay. A mouse model of xenotransplanted C26 mouse colon cancer was established. The inhibitory effects of Pll0 and eisplatin at different concentrations on C26 xenotransplanted tumors were assessed. Results P110 enhanced the inhibitory effect of cisplatin on proliferation of HCT-116 cells. By treated with 20 μmol/LP110 ±10, 30, 90 μmoL/L cisplatin, the proliferation inhibitory rates were （43.3± 3.2） %, （46.4± 4.6 ） % and （47.6 ± 5.8 ） %, respectively, significantly higher than that in the cisplatin group （P 〈0.05）. 20μmol/L PllO ＋ 10μmol/L cisplatin effectively killed HCT-116 cells, whereas with less toxicity to HUVEC cells. The tumor inhibition rates in mice of Pll0 （25 mg/kg, 50 mg/kg, 100 mg/kg） plus cisplatin （ 1 mg/kg） were 23.0%, 30.4% and 34.2%, respectively. While, the tumor inhibition rates in mice of the cisplatin group （ 1 mg/kg） was 22.7%. Compared with cisplatin at the same concentration, the tumor inhibition rates in mice of the Pll0 plus eisplatin groups were all increased. Conclusions Pll0 can enhance the growth inhibitory effects of cisplatin on HCT-116 cells and C26 xenotransplanted tumors in mice. P110 plus cisplatin can reduce the effective dose of cisplatin and decrease the toxicity of cisplatin.