Abstract：
OBJECTIVE: This study was designed to compare the antitumor effects of anti-human MUC1 monoclonal antibody with those of anti-human CA199 monoclonal antibody coupled with drug-loaded polybutylcyanoacrylate nanoparticles on human pancreatic cancer cell lines and pancreatic cancer-bearing model animals and to screen more efficient targeting molecules.
METHODS: Gemcitabine-loaded nanospheres were prepared by emulsion polymerization (GEM-PBCA-NP), and then, anti-MUC1 monoclonal antibody was coupled with GEM-PBCA-NP (MUC1-GEM-PBCA-NP), and anti-human CA199 monoclonal antibody was coupled with GEM-PBCA-NP (CA199-GEM-PBCA-NP), using the chemical crosslinking method. The cell-killing rates were detected using MTT assay. The changes in the tumor cell cycle and apoptosis after treatment were detected using flow cytometry. Then, the subcutaneous planting method was adopted to establish an animal model of pancreatic cancer: two nanometer microspheres were injected into the body of nude mice via the tail vein; the tumor suppression effect was detected after treatment; then, the groups were compared.
RESULTS: In vitro, the cell-killing rate of each experimental group was significantly different from that of the control group (P < 05). The MUC1-GEM-PBCA-NP group had a significantly higher cell-killing rate than the other groups (P < 05). The apoptosis rate of the MUC1-GEM-PBCA-NP treatment group was significantly higher than that of other groups (P < 05). In vivo, the tumor inhibition rate of the MUC1-GEM-PBCA-NP treatment group was 72.69% ± 4.29%, which was significantly higher than those of other groups (P < 0.05). The tumor inhibition rate of the CA199-GEM-PBCA-NP treatment group was 56.58% ± 5.11%, which was significantly higher than those of other control groups (P < 0.05). At the end of treatment, the average tumor mass of the MUC1-GEM-PBCA-NP treatment group was 433.55 ± 12.49 mg, which was significantly lower than those of other groups (P < 0.05).
CONCLUSIONS: Compared with CA199-GEM-PBCA-NP, MUC1-GEM-PBCA-NP is more effective in vitro and in vivo. MUC1 could be a target molecule in treating pancreatic cancer.
METHODS: Gemcitabine-loaded nanospheres were prepared by emulsion polymerization (GEM-PBCA-NP), and then, anti-MUC1 monoclonal antibody was coupled with GEM-PBCA-NP (MUC1-GEM-PBCA-NP), and anti-human CA199 monoclonal antibody was coupled with GEM-PBCA-NP (CA199-GEM-PBCA-NP), using the chemical crosslinking method. The cell-killing rates were detected using MTT assay. The changes in the tumor cell cycle and apoptosis after treatment were detected using flow cytometry. Then, the subcutaneous planting method was adopted to establish an animal model of pancreatic cancer: two nanometer microspheres were injected into the body of nude mice via the tail vein; the tumor suppression effect was detected after treatment; then, the groups were compared.
RESULTS: In vitro, the cell-killing rate of each experimental group was significantly different from that of the control group (P < 05). The MUC1-GEM-PBCA-NP group had a significantly higher cell-killing rate than the other groups (P < 05). The apoptosis rate of the MUC1-GEM-PBCA-NP treatment group was significantly higher than that of other groups (P < 05). In vivo, the tumor inhibition rate of the MUC1-GEM-PBCA-NP treatment group was 72.69% ± 4.29%, which was significantly higher than those of other groups (P < 0.05). The tumor inhibition rate of the CA199-GEM-PBCA-NP treatment group was 56.58% ± 5.11%, which was significantly higher than those of other control groups (P < 0.05). At the end of treatment, the average tumor mass of the MUC1-GEM-PBCA-NP treatment group was 433.55 ± 12.49 mg, which was significantly lower than those of other groups (P < 0.05).
CONCLUSIONS: Compared with CA199-GEM-PBCA-NP, MUC1-GEM-PBCA-NP is more effective in vitro and in vivo. MUC1 could be a target molecule in treating pancreatic cancer.
摘要：
目的：本研究旨在比较抗人MUC1单克隆抗体和抗人CA199单克隆抗体结合聚氰基丙烯酸丁酯纳米粒对人胰腺癌细胞系和胰腺癌模型动物的抗肿瘤作用，并筛选更有效的靶向分子。
方法：通过乳液聚合（GEM-PBCA-NP）制备载有吉西他滨的纳米球，然后,抗MUC1单克隆抗体与GEM-PBCA-NP（MUC1-GEM-PBCA-NP）偶联，抗人CA199单克隆抗体与GEM-PBCA-NP（CA199-GEM-PBCA-NP）偶联，使用化学交联方法。使用MTT法检测细胞杀伤率。流式细胞术检测治疗后肿瘤细胞周期和细胞凋亡的变化。然后，采用皮下种植法建立胰腺癌动物模型:经尾静脉注射两个纳米微球到裸鼠体内,治疗后检测抑瘤效果;各组进行比较。
结果：体外，各实验组细胞杀伤率与对照组比较差异有统计学意义(P<0.05)。MUC1-GEM-PBCA-NP组的细胞杀伤率明显高于其他组（P<05）。MUC1-GEM-PBCA-NP治疗组的凋亡率明显高于其他组（P<05）。在体内,MUC1-GEM-PBCA-NP治疗组的抑瘤率为72.69%±4.29%,显著高于其他组(P<0.05)。CA199-GEM-PBCA-NP治疗组的抑瘤率为56.58%±5.11%,显著高于其他对照组(P<0.05)。在治疗结束时,MUC1-GEM-PBCA-NP治疗组的平均肿瘤质量为433.55±12.49mg，显著低于其他组(P<0.05)。
结论：与CA199-GEM-PBCA-NP相比，MUC1-GEM-PBCA-NP在体外和体内更有效。MUC1可能是治疗胰腺癌的靶分子。
方法：通过乳液聚合（GEM-PBCA-NP）制备载有吉西他滨的纳米球，然后,抗MUC1单克隆抗体与GEM-PBCA-NP（MUC1-GEM-PBCA-NP）偶联，抗人CA199单克隆抗体与GEM-PBCA-NP（CA199-GEM-PBCA-NP）偶联，使用化学交联方法。使用MTT法检测细胞杀伤率。流式细胞术检测治疗后肿瘤细胞周期和细胞凋亡的变化。然后，采用皮下种植法建立胰腺癌动物模型:经尾静脉注射两个纳米微球到裸鼠体内,治疗后检测抑瘤效果;各组进行比较。
结果：体外，各实验组细胞杀伤率与对照组比较差异有统计学意义(P<0.05)。MUC1-GEM-PBCA-NP组的细胞杀伤率明显高于其他组（P<05）。MUC1-GEM-PBCA-NP治疗组的凋亡率明显高于其他组（P<05）。在体内,MUC1-GEM-PBCA-NP治疗组的抑瘤率为72.69%±4.29%,显著高于其他组(P<0.05)。CA199-GEM-PBCA-NP治疗组的抑瘤率为56.58%±5.11%,显著高于其他对照组(P<0.05)。在治疗结束时,MUC1-GEM-PBCA-NP治疗组的平均肿瘤质量为433.55±12.49mg，显著低于其他组(P<0.05)。
结论：与CA199-GEM-PBCA-NP相比，MUC1-GEM-PBCA-NP在体外和体内更有效。MUC1可能是治疗胰腺癌的靶分子。
