蛋白激酶D1在调节口腔鳞癌细胞增殖、凋亡及药物敏感性中的作用
Role of protein kinase D1 in regulating the growth, apoptosis and drug sensitivity of oral squamous carcinoma cells
作者：王京楠,樊亚萍,陈娇,冯云,崔博淼,李小英,王利伟,陈红利,张平,吴红崑
Author：Wang Jingnan,Fan Yaping,Chen Jiao,Feng Yun,Cui Bomiao,Li Xiaoying,Wang Liwei,Chen Hongli,Zhang Ping,Wu Hongkun
收稿日期：2019-03-16 年卷（期）页码：2019,37(6):583-583-588
期刊名称：华西口腔医学杂志
Journal Name：West China Journal of Stomatology
关键字：蛋白激酶D1,口腔鳞癌,紫杉醇,耐药性,
Key words：protein kinases D1,oral squamous carcinoma,paclitaxel,multi-drug resistance,
基金项目：国家自然科学基金(81372892)
中文摘要
目的 探讨蛋白激酶D1（PKD1）在人口腔鳞癌细胞SCC-25生长、凋亡及化疗药物敏感性中的作用和机制。方法 转染control-shRNA和PKD1-shRNA质粒,建立PKD1基因沉默的SCC-25细胞系;CCK-8及流式细胞术检测PKD1基因沉默后细胞的增殖、凋亡及细胞对化疗药物紫杉醇的敏感性;Western blot检测凋亡相关蛋白Bax、Bcl-2及多药耐药蛋白P-gp的表达变化。结果 PKD1在口腔肿瘤细胞SCC-25、CAL-27、SACC-83中呈现高表达;PKD1基因沉默后SCC-25细胞内抗凋亡蛋白Bcl-2表达显著降低,细胞生长受到抑制,凋亡增加;多药耐药蛋白P-gp表达下调,紫杉醇半数抑制浓度及耐药指数明显降低。结论 PKD1通过调控SCC-25细胞内凋亡相关蛋白表达和多药耐药蛋白P-gp表达,调控SCC-25生长、凋亡和对药物敏感性,是口腔鳞癌细胞生物治疗潜在靶点。
英文摘要
ObjectiveThis study aimed to investigate the role of protein kinase D (PKD)1 in regulating the growth, apoptosis, and drug sensitivity of the squamous carcinoma cell line SCC-25.MethodsThe SCC-25 cell line was transfected with either the control-shRNA or PKD1-shRNA plasmids. The stable transfected cells were selected, and the efficiency of PKD1 knockdown was detected by Western blot. The growth and apoptosis of SCC-25 were analyzed with a cell counting kit-8 (CCK8) and flow cytometry. The 50% inhibitory concentrations (IC50) of paclitaxel in the control and PKD1 knockdown cell lines were detected by CCK-8. The expression levels of Bax, Bcl-2, and P-gp were detected by Western blot.ResultsPKD1 was constitutively expressed and phosphorylated in various cancer cell lines. Inhibiting the expression of PKD1 in SCC-25 cells by RNA interference could inhibit the growth and promote the apoptosis of SCC-25 cells via downregulating Bcl-2 expression. Additionally, inhibiting PKD1 expression could downregulate the expression of P-gp, thereby decreasing both the IC50 and resistance index of paclitaxel.ConclusionPKD1 plays an important role in regulating the biobehavior of SCC-25. It is a potential therapeutic target for oral squamous carcinoma.
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