CDK6 在胃癌中的表达及 CDK4/6 抑制剂 PD-0332991 对胃癌细胞功能的影响。
Expression of CDK6 in Stomach Cancer and the Effect of CDK4/6 Inhibitor PD-0332991 on the Function of Stomach Cancer Cells.
机构信息
Department of Laboratory Medicine, School of Medicine of Yangzhou Univerisity, Yangzhou, Jiangsu Province, China 225000.
Medical Research Center, Clinical Medical College, Yangzhou University, Yangzhou, Jiangsu Province, China 225000.
出版信息
Comput Math Methods Med. 2022 Apr 30;2022:2402567. doi: 10.1155/2022/2402567. eCollection 2022.
OBJECTIVE
To study the expression and prognostic value of CDK6 in stomach cancer and the function of CDK4/6 inhibitor PD-0332991 on the proliferation of stomach cancer cells.
METHODS
Immunohistochemistry was used to detect the expression of CDK6 in stomach cancer tissues and adjacent normal tissues and to analyze the effect of CDK6 on clinicopathological parameters of stomach cancer patients. Kaplan-Meier plotter was employed to study the relationship between CDK6 and overall survival in stomach cancer. Western blot and RT-PCR were used to detect protein and gene expression of CDK6 in different cells. The effects of CDK4/6 inhibitor PD-0332991 on apoptosis and aging of stomach cancer cells were detected by flow cytometry and -galactosidase aging staining assay. The effects of CDK4/6 inhibitor PD-0332991 on the invasion and migration of stomach cancer cells were explored by the wound healing experiment and the Transwell experiment. The supernatant of stomach cancer cells was collected, and the effect of CDK4/6 inhibitor PD-0332991 on tumor markers of stomach cancer cells was detected by biochemical immunoassay.
RESULTS
(1) CDK6 was highly expressed in stomach cancer tissues and cells. (2) Abnormally elevated CDK6 expression results in shorter survival in stomach cancer patients. (3) CDK4/6 inhibitor PD-0332991 could block the proliferation of stomach cancer cells, but not stomach epithelial proliferation. PD-0332991 could inhibit the secretion of pro-GRP by MGC 823. (4) PD-0332991 could advance the development of the apoptosis and senescence of stomach cancer cells and suppressed the invasion and migration of stomach cancer cells.
CONCLUSION
CDK6 expression is elevated in gastric cancer, and the CDK4/6 inhibitor PD-0332991 can remarkably promote apoptosis and senescence of stomach cancer cells and effectively inhibit the migration and invasion of stomach cancer cells.
目的
研究 CDK6 在胃癌中的表达及其预后价值，以及 CDK4/6 抑制剂 PD-0332991 对胃癌细胞增殖的作用。
方法
采用免疫组织化学法检测胃癌组织及癌旁正常组织中 CDK6 的表达，分析 CDK6 对胃癌患者临床病理参数的影响。采用 Kaplan-Meier plotter 研究 CDK6 与胃癌患者总生存的关系。采用 Western blot 和 RT-PCR 检测不同细胞中 CDK6 的蛋白和基因表达。通过流式细胞术和β-半乳糖苷酶衰老染色实验检测 CDK4/6 抑制剂 PD-0332991 对胃癌细胞凋亡和衰老的影响。通过划痕实验和 Transwell 实验探讨 CDK4/6 抑制剂 PD-0332991 对胃癌细胞侵袭和迁移的影响。收集胃癌细胞上清液，采用生化免疫法检测 CDK4/6 抑制剂 PD-0332991 对胃癌细胞肿瘤标志物的影响。
结果
（1）CDK6 在胃癌组织和细胞中高表达。（2）CDK6 异常高表达导致胃癌患者生存时间缩短。（3）CDK4/6 抑制剂 PD-0332991 可阻断胃癌细胞的增殖，但不阻断胃上皮细胞的增殖。PD-0332991 可抑制 MGC 823 分泌 pro-GRP。（4）PD-0332991 可促进胃癌细胞凋亡和衰老，抑制胃癌细胞侵袭和迁移。
结论
CDK6 在胃癌中表达上调，CDK4/6 抑制剂 PD-0332991 可显著促进胃癌细胞凋亡和衰老，有效抑制胃癌细胞的迁移和侵袭。
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