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PD98059联合紫杉醇对人胃印戒细胞癌细胞增殖和凋亡的影响 Δ

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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（新疆医科大
学附属肿瘤医院消化内科，乌鲁木齐 830011）

中图分类号 R735.2 文献标志码 A 文章编号 1001-0408（2020）06-0703-05
DOI 10.6039/j.issn.1001-0408.2020.06.13

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48 h后的细胞增殖情况，并计算增殖抑制率；采用流式细胞术、Western blotting、Transwell法分别检测紫杉醇、PD98059
以及两药联合作用48 h或24 h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（1 μg/mL）、PD98059（5、20、40 μmol/L）以及两药（1 μg/mL+5、20、40 μmol/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（1 μg/mL）、PD98059（40 μmol/L）以及
两药（1 μg/mL+40 μmol/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KATO Ⅲ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。
关键词 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
路；KATO Ⅲ细胞

Effects of PD98059 Combined with Paclitaxel on Cell Proliferation and Apoptosis of Human Gastric Signet
Ring Cell Carcinoma Cells
Saifuding·Keyoumu，Bulibu·Jilisihan，MA Lanying，LI Na，Abulajiang·Tayier，LIU Cuiyun，SHE Ling，TANG
Yong（Dept. of Digestive System，the Affiliated Tumor Hospital of Xinjiang Medical University，Urumqi
830011，China）

ABSTRACT OBJECTIVE：To investigate the effects of MEK/ERK pathway specific inhibitor PD98059 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 PD98059 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 PD98059 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 PD98059 alone group （P＜0.05）. CONCLUSIONS：Paclitaxel and PD98059 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 PD98059 alone.
KEYWORDS Human grastric signet ring cell carcinoma；Paclitaxel；PD98059；Proliferation；Apoptosis；Apoptosis related
protein；Migration；MEK/ERK pathway；KATO Ⅲ cells

胃印戒细胞癌是基于微观组织形态学分型的一种
Δ 基金项目：新疆维吾尔自治区自然科学基金资助项目（No.2016-
D01C362） 特殊病理类型的胃癌，其镜检可见肿瘤细胞胞质丰富、
＊副主任医师，硕士。研究方向：消化系统肿瘤诊治。电话： 充满黏液，细胞核被挤压于胞质一侧呈“印戒”样 [1-2] 。近
0991-7819112。E-mail：592996737@qq.com
年来，随着幽门螺旋杆菌根治术的应用，胃癌的发病率
# 通信作者：主任医师，硕士生导师。研究方向：消化系统肿瘤诊
虽有所下降，但胃印戒细胞癌的发病率却有所上升，占
治。电话：0991-7819116。E-mail：ae717ty@qq.com

中国药房 2020年第31卷第6期 China Pharmacy 2020 Vol. 31 No. 6 ·703 ·