PD98059联合紫杉醇对人胃印戒细胞癌细胞增殖和凋亡的影响
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篇名: | PD98059联合紫杉醇对人胃印戒细胞癌细胞增殖和凋亡的影响 |
TITLE: | Effects of PD 98059 Combined with Paclitaxel on Cell Proliferation and Apoptosis of Human Gastric Signet Ring Cell Carcinoma Cells |
摘要: | 目的:探讨丝裂原激活蛋白激酶激酶/细胞外信号调节激酶(MEK/ERK)通路特异性抑制剂PD98059联合紫杉醇对人胃印戒细胞癌细胞增殖和凋亡的影响。方法:以人胃印戒细胞癌KATOⅢ细胞为对象,采用CCK-8法检测紫杉醇、PD98059以及两药联合作用48h后的细胞增殖情况,并计算增殖抑制率;采用流式细胞术、Westernblotting、Transwell法分别检测紫杉醇、PD98059以及两药联合作用48h或24h后的细胞凋亡、凋亡相关蛋白[分裂型胱天蛋白酶3(Cleaved-caspase-3)]表达和细胞迁移情况。结果:经紫杉醇(1μg/mL)、PD98059(5、20、40μmol/L)以及两药(1μg/mL+5、20、40μmol/L)联合作用后,各给药组细胞的增殖抑制率均显著升高,且联用组显著高于紫杉醇、PD98059同剂量单用组(P<0.05)。经紫杉醇(1μg/mL)、PD98059(40μmol/L)以及两药(1μg/mL+40μmol/L)联合作用后,紫杉醇组和两药联用组细胞的早期、晚期凋亡率以及Cleave-caspased-3蛋白的表达量均显著升高,且联用组显著高于紫杉醇、PD98059单用组(P<0.05);各给药组的细胞迁移数均显著减少,且联用组显著少于紫杉醇、PD98059单用组(P<0.05)。结论:紫杉醇、PD98059均可抑制人胃印戒细胞癌KATOⅢ细胞的增殖和迁移,且紫杉醇还可促进该细胞的凋亡及凋亡相关蛋白的表达,上述作用可能与抑制MEK/ERK通路有关。两药联用的效果优于紫杉醇或PD98059单用。 |
ABSTRACT: | OBJECTIVE:To investiga te the effects of MEK/ERK pathway specific inhibitor PD 98059 combined with paclitaxel on the proliferation and apoptosis of human gastric signet ring cell carcinoma (SRCC)cells. METHODS :Using human SRCC KATO Ⅲ cells as object ,CCK-8 assay was used to detect cell proliferation after treated with paclitaxel ,PD98059 and two drug combination for 48 h,and the proliferation rate was calculated. Flow cytometry ,Western blotting and Transwell assay were used to detect the cell proliferation ,the expression of apoptosis related protein (Cleaved-caspase-3)and cell migration after treated with paclitaxel,PD98059 and two drug combination for 48 or 24 h. RESULTS :After treated with paclitaxel (1 μg/mL),PD98059(5, 20,40 μmol/L)and two drug combination (1 μg/mL+5,20,40 μmol/L),the proliferation rate of cells was increased significantly in administration groups ,and the combination groups were significantly higher than paclitaxel and PD 98059 alone groups (P< 0.05). After treated with paclitaxel (1 μg/mL),PD98059(5,20,40 μmol/L)and two drug combination (1 μg/mL+40 μmol/L), early and late apoptosis rate ,the protein expression of Cleaved-caspase- 3 were significantly increased in paclitaxel group and combination group ;combination group was significantly higher than paclitaxel and PD 98059 alone group (P<0.05). The number of migrated cells in administration groups were reduced significantly ,and the combination group was significantly lower than paclitaxel and PD 98059 alone group (P<0.05). CONCLUSIONS :Paclitaxel and PD 98059 can inhibit the proliferation and migration of human SRCC KATO Ⅲ cells,paclitaxel can also promote the apoptosis and the expression of apoptosis related protein,which may be related to the inhibition of MEK/ERK pathway. The effect of the combination of the two drugs is better than paclitaxel or PD 98059 alone. |
期刊: | 2020年第31卷第06期 |
作者: | 赛福丁·柯尤木,布力布·吉力斯汉,马兰英,李娜,阿布拉江·塔依尔,刘翠云,舍玲,唐勇 |
AUTHORS: | Saifuding· Keyoumu,Bulibu·Jilisihan,MA Lanying,LI Na,Abulajiang·Tayier,LIU Cuiyun,SHE Ling,TANG Yong |
关键字: | 人胃印戒细胞癌;紫杉醇;PD98059;增殖;凋亡;凋亡相关蛋白;迁移;丝裂原激活蛋白激酶激酶/细胞外信号调节激酶通 |
KEYWORDS: | Human grastric signet ring cell carcinoma ;Paclitaxel;PD98059;Proliferation;Apoptosis;Apoptosis related |
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