吉西他滨联合西妥昔单抗对三阴乳腺癌细胞转移相关基质金属蛋白酶-9(MMP-9)活性的影响

目的:探讨吉西他滨联合西妥昔单抗对三阴乳腺癌细胞增殖、迁移、侵袭的影响,并对可能的机制进行初步的探究。方法:将实验分为西妥昔单抗组(150μg·mL^-1)、吉西他滨联合用药组(西妥昔单抗150μg·mL^-1,吉西他滨2.8μg·mL^-1)。通过MTT、Transwell实验检测联合用药对MDA-MB-231细胞增殖、迁移、侵袭能力的影响,Western blotting实验检测合用药对MDA-MB-231细胞MMP-9、TIMP-1、p-IkB、NF-kB-p65表达水平的影响。结果:吉西他滨联合西妥昔单抗作用MDA-MB-231细胞后,其生长被不同程度的抑制,抑制率随吉西他滨浓度的增加而增高(P<0.05);联合用药组MDA-MB-231细胞迁移、侵袭数目明显减少(P<0.05),同时MMP-9、p-IkB、NF-kB-p65的表达含量降低,TIMP-1表达含量增加。结论:吉西他滨联合西妥昔单抗对三阴乳腺癌细胞增殖、侵袭、迁移具有抑制作用,并明显抑制MMP-9的表达,其机制可能是通过抑制NF-kB通路实现。

Effect of gemcitabine combined with cetuximab on the activity of matrix metalloprote-inase-9 (MMP-9) of triple-negative breast cancer

OBJECTIVE To investigate the effects of gemcitabine combined with cetuximab on proliferation, migration and invasion of triple-negative breast cancer cells, and to explore its possible mechanism.METHODS The subjects were divided into cetuximab group (150 μg·mL^-1), gemcitabine combination group (cetuximab 150 μg·mL^-1, gemcitabine 2.8 μg·mL^-1). MTT and Transwell assay were used to detect the effect of combination therapy on the proliferation, migration and invasion of MDA-MB-231 cells. Western blotting assay was used to detect the expression of MMP-9, TIMP-1, p-IkB and NF-kB-p65 in MDA-MB-231 cells. RESULTS Gemcitabine combined with cetuximab inhibited the growth of MDA-MB- 231 cells in different degrees, and the inhibition rate increased with the increase of gemcitabine concentration (P<0.05). The number of migration and invasion of MDA-MB-231 cells in the combination group was significantly decreased (P<0.05), while the expression levels of MMP-9, p-IkB and NF-kB-p65 were decreased, and the expression of TIMP-1 was increased.CONCLUSION Gemcitabine combined with cetuximabcan inhibit the proliferation, invasion and migration of TNBC cells and inhibit the expression of MMP-9, and the mechanism may be related with inhibition of NF-kB pathway.