SphK1在人胃癌裸鼠移植瘤生长中的作用研究  

The role of SphK1 in the growth of human gastric cancer xenograft in nude mice

作　　者：黄广淸 朱正秋[1] 苗怡然[2] 单海霞[1] 

机构地区：[1]徐州医学院附属医院肿瘤内科,江苏徐州221004 [2]徐州市肿瘤医院肿瘤内科,江苏徐州221005

出　　处：《徐州医学院学报》2014年第11期789-793,共5页Acta Academiae Medicinae Xuzhou

基　　金：江苏省“六大人才高峰”项目（D032）;江苏省卫生厅指导性科研课题（Z201016）.

摘　　要：目的研究鞘氨醇激酶-1（sphingosine kinase-1，SphK1）在人胃癌裸鼠移植瘤生长中的作用，并探讨其机制。方法将培养至对数生长期的SGC7901（人胃癌）细胞注射于裸鼠皮下，建立人胃癌裸鼠移植瘤模型，建模成功后将裸鼠随机分为4组，每组8只，分别用生理盐水、SKI—Ⅱ、顺铂（DDP）、SKI-Ⅱ联合DDP对移植瘤进行干预，每周腹腔注射1次，共3次。定期测量肿瘤体积，绘制肿瘤时间一体积生长抑制曲线。在治疗结束后的第7天脱颈处死全部裸鼠，取下瘤体组织，Westernblot法及免疫组化法检测瘤体内SphK1、Bax、Bc1-2蛋白的表达情况，原位末端标记染色（TUNEL）法检测肿瘤组织细胞凋亡。结果成功构建了人胃癌裸鼠移植瘤模型，SKI-Ⅱ单独及联合顺铂应用于荷瘤裸鼠后，均能通过抑制SphKl蛋白的表达增加Bax／Bcl-2的比值，且联合用药组能较SKI-Ⅱ组和顺铂组更显著地减少肿瘤组织SphKl、Bcl-2蛋白的表达（P〈0．05），并增加Bax蛋白的表达（P〈0．05）。SKI-Ⅱ联合DDP组更明显地抑制了肿瘤的生长（P〈0．05）。结论SphKl通过调节Bax／Bel-2的比值起到影响胃癌生长的作用，胃癌细胞中SphKl的表达被抑制后，通过引起Bax／Bel-2比值的升高，进而产生了诱导胃癌细胞凋亡、抑制肿瘤生长的作用。SphKl的特异性抑制剂SKI-Ⅱ不仅可单独应用达到抑制胃癌生长的目的，且与DDP联合应用可发挥协同抗肿瘤作用。Objective To investigate the role of SphK1 in the growth of human gastric cancer xenograft in nude mice and to explore its mechanism. Mechods Human gastric cancer cell SGC7901 cells were cultured to exponential phase of growth and then transplanted under the skin of BALB/c nude mice to develop the tumor model of human gastric cancer. After the model was successfully established, 38 mice were randomly divided into four groups： normal saline （NS） control group, cisplantin （DDP） group, SKI - Ⅱ group, SKI - Ⅱ I combined with DDP group. All rats were given intraper- itoneal injection of drugs once a week for 3 times. The tumor mass volume was observed every 3 days and the inhibition rate of tumor growth was also caleulated. All nude mice in eaeh group were killed at the 7th day after the injeetion of drugs and the tumor was dislodged. Western blot and immunohistochemistry staining were used to detect the protein expression of SphK1, Bax and Bcl - 2. The apoptosis of tumor was measured by terminal dUTP niekend labeling （TUNEL）. Results Human gastrie cancer xenograft in nude mice was suceessfully established. When SKI - Ⅱ alone or combined with DDP was used on nude mice with gastric cancer xenograft, the ratio of Bax/Bcl -2 was increase by inhibiting the expression of SphK1 protein. Compared with SKI - Ⅱgroup and DDP group, SKI - Ⅱ combined with DDP group showed stronger inhibiting effect on the expression of SphK1 and Bcl - 2 proteins in the tumor tissure （ P 〈 0.05 ） and inereased expression of Bax protein （ P 〈 0.05 ）. SKI - Ⅱ combincd with DDP group showed stronger effect in hihibking tumor growth than SKI - Ⅱ group and DDP group （P 〈 0.05 ）. Conclusions SphK1 plays a role in affecting the growth of gastrie eancer by adjusting the ratio of Bax/Bel - 2, the ratio of Bax/Bcl - 2 increases via its expression is suppressed in gastric eancer cells, and then induces apoptosis and inhibites tumor growth. SKI - Ⅱ can not only be used to inhibit the growth of gastrie cancer ob

关 键 词：胃癌 SKI-Ⅱ SphK1 裸鼠 BAX/BCL-2 

分 类 号：R735.2[医药卫生—肿瘤]