百里醌对大肠癌生长和转移的抑制作用

摘要

Objective To investigate the anti - proliferation and anti - metastasis effects of thymoquinone on the colon cancer. Methods After human colon cancer cell line SW480 was treated with thymoquinone, the cellular proliferation was detected by cell counting kit - 8 ( CCK - 8) assay. SW480 cells morphological changes were observed under the fluorescence microscopy after DAPI staining. The effects of thymoquinone on the migration and invasion of SW480 cells were examined by using wound assay and matrigel counting. Western blotting was used to detect the protein expression in colon cancer cells. SW480 cells were injected subcutaneously into nude mice to establish colon xenograft tumors. The tumor weight was weighed at the termination of experiment, and the tumor growth inhibition rate was calculated after mice were sacrificed. Immunohistochemistry was used to detect the positive expression of Ki - 67 and Mucin - 4 in the xenograft tumors. Results Thymoquinone induced a higher percentage of growth inhibition in colon cancer cell line SW480 than that of control,and thymoquinone induced typical features of apoptosis in SW480 cells. Thymoquinone significantly suppressed the migration and invasion of SW480 cells. The expression of Mucin - 4, HER - 2 and phosphorylation of FAK was down - regulated in SW480 cells after treatment of thymoquinone. The final tumor weight showed significant decrease in the thymoquinone group compared with control ( P < 0.05). Furthermore, the positive expression of Ki -67 and Mucin -4 was decreased in tumors after treatment of thymoquinone. Conclusion Thymoquinone exerts anti - proliferative and anti - metastatic activity in colon cancer,which may be related to down - regulation of Mucin - 4 protein.%目的 探讨百里醌对大肠癌生长及转移的影响及其机制.方法 百里醌作用大肠癌细胞株SW480后,cell counting kit -8(CCK -8)法检测细胞增殖；荧光显微镜下观察细胞形态；划痕试验和Transwell小室实验分别测定大肠癌细胞体外迁移和侵袭能力；用Western blotting检测大肠癌细胞中Mucin -4、HER -2和FAK蛋白表达；建立起裸鼠大肠癌皮下移植模型,观察百里醌对裸鼠大肠癌移植瘤生长的影响；免疫组织化学法检测肿瘤组织中Ki-67和Mucin -4阳性表达.结果 与对照组相比较,百里醌可显著抑制体外大肠癌SW480细胞生长、迁移和侵袭,并明显诱导细胞凋亡；百里醌可呈显著下调大肠癌细胞中Mucin -4和HER -2的表达,并抑制FAK磷酸化；百里醌可显著抑制裸鼠大肠癌皮下移植瘤生长；百里醌可明显降低大肠癌肿瘤组织中Ki- 67和Mucin -4的阳性表达.结论 百里醌可显著抑制大肠癌生长和转移,该作用可能通过抑制Mucin -4蛋白表达而实现.