CAJ | 학술논문

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。
목적：관찰새래석포연합NK세포대라서인간암세포SMMC-7721피하이식류생장적영향，병탐토기가능적작용궤제。방법선택라서40지，제비인간암세포SMMC-7721이식류모형，수궤분위대조조、NK세포조、새래석포조급연합간예조각10지。 NK세포조류내주사NK세포현액0．6 mL，매7 d주사1차，공주사5차；새래석포조종접충후제3천기급여새래석포100 mg/kg관위，매천1차，련속35 d；연합간예조동시급여새래석포화NK세포，급약제량급도경여단용조상동；대조조관위화류내주사등량생리염수。35 d후절취이식류조직계산체적，칭취류질량，병계산억류솔；TUNEL법평개종류세포조망정황，면역조화법검측종류내VEGF、Bax、Bcl-2、caspase-3、Ki-67、NF-κB적양성표체。결과연합간예조이식류체적、종류질량균명현저우단용조（ P균＜0．05），억류솔、조망지수명현고우단용조（ P균＜0．05）。연합간예조이식류중VEGF、Bcl-2、NF-κB、Ki-67표체명현저우단용조（ P균＜0．05），Bax、caspase-3표체명현고우단용조（P균＜0．05）。결론새래석포연합NK세포가명현억제라서인간암세포SMMC-7721피하이식류적생장；기작용궤제가능시통과촉진조망급련통로상Bax、caspase-3적표체，억제VEGF、Bcl-2、NF-κB、Ki-67적표체이실현。
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 inocula-tion, 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 ex-cised 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 interven-tion 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 be related to inhibiting the expression of VEGF , Bcl-2, NF-κB, Ki-67 and promoting the expression of Bax and caspase-3.