塞来昔布联合 NK 细胞对裸鼠人肝癌皮下移植瘤生长的影响

目的：观察塞来昔布联合NK细胞对裸鼠人肝癌细胞SMMC-7721皮下移植瘤生长的影响，并探讨其可能的作用机制。方法选择裸鼠40只，制备人肝癌细胞SMMC-7721移植瘤模型，随机分为对照组、NK细胞组、塞来昔布组及联合干预组各10只。 NK细胞组瘤内注射NK细胞悬液0．6 mL，每7 d注射1次，共注射5次；塞来昔布组从接种后第3天起给予塞来昔布100 mg/kg灌胃，每天1次，连续35 d；联合干预组同时给予塞来昔布和NK细胞，给药剂量及途径与单用组相同；对照组灌胃和瘤内注射等量生理盐水。35 d后切取移植瘤组织计算体积，称取瘤质量，并计算抑瘤率；TUNEL法评价肿瘤细胞凋亡情况，免疫组化法检测肿瘤内VEGF、Bax、Bcl-2、caspase-3、Ki-67、NF-κB的阳性表达。结果联合干预组移植瘤体积、肿瘤质量均明显低于单用组（ P均＜0．05），抑瘤率、凋亡指数明显高于单用组（ P均＜0．05）。联合干预组移植瘤中VEGF、Bcl-2、NF-κB、Ki-67表达明显低于单用组（ P均＜0．05），Bax、caspase-3表达明显高于单用组（P均＜0．05）。结论塞来昔布联合NK细胞可明显抑制裸鼠人肝癌细胞SMMC-7721皮下移植瘤的生长；其作用机制可能是通过促进凋亡级联通路上Bax、caspase-3的表达，抑制VEGF、Bcl-2、NF-κB、Ki-67的表达而实现。

Combined effects of celecoxib and NK Cells on growth of SMMC-7721 hepatocellar carcinoma xenografts in nude mice

Objective To evaluate the inhibitory effect and its mechanism of celecoxib combined with NK cells on the growth of implanted human liver caner cell line SMMC-7721 in nude mice.Methods Forty nude mice were inoculated the hepatoma cell line SMMC-7721, and then were randomly divided into the control group , NK cells group, celecoxib group and combined intervention group with 10 rats in each group.in the NK cells group, the mice were intratumorally injected NK cell suspension 0.6 mL, every 7 d for one time, for 5 times;in the celecoxib group, from the third day after inoculation, the mice were treated with celecoxib 100 mg/kg orally, 1 time a day for 35 days;in the combined intervention group , mice were given celecoxib and NK cells , whose dosage and way were the same as that of the single group; in the control group, mice were given oral and intratumoral injection of normal saline .Thirty-five days later , the mice′s tumors were excised for further analysis .The tumors were weighed and the tumor inhibitory rate was calculated .Apoptosis was measured by using a terminal deoxynucleotidyl transferase-mediated nick-end labeling （ TUNEL） assay.The protein levels of vascular endothelial growth factor （VEGF）, Bax, Bcl-2, caspase-3, Ki-67 and NF-κB were detected by immunohistochemistry . Results The tumor volume , tumor mass and apoptosis index of the combined intervention group were significantly lower than those of the NK cells group and celecoxib group （all P〈0.05）.The tumor inhibition rate was 28.84% in the NK cells group and 50.42%in the celecoxib group which was significantly lower than that 87.59%in the combined intervention group.The expression of VEGF, Bcl-2, NF-κB and Ki-67 was significantly lower, but the expression of Bax and caspase-3 was significantly higher in the combined intervention group than that of the other single groups （all P〈0.05）.Conclusion Celecoxib combined with NK cells can induce the apoptosis of SMMC-7721 cells and inhibit the growth of xenografts, whose mechanism may