姜黄素与吉非替尼联合应用对胃癌SGC-7901细胞增殖及裸鼠移植瘤生长的影响

目的：探讨不同浓度的姜黄素与吉非替尼联合应用对体内胃癌裸鼠移植瘤及体外胃癌细胞SGC-7901生长的影响。方法：将胃癌细胞SGC-7901制成细胞悬液后接种于裸鼠皮下,制备胃癌裸鼠模型。将裸鼠模型随机分为生理盐水组及姜黄素与吉非替尼联合应用低剂量组、中剂量组、高剂量组,腹腔注射给药,每周一次。用药4次后,处死裸鼠,剥取肿瘤组织,称取质量,计算肿瘤抑制率。用免疫组织化学方法检测肿瘤组织中c-myc的表达。低剂量、中剂量、高剂量姜黄素与吉非替尼联合作用SGC-7901细胞,Western blot方法检测细胞内c-myc的表达,MTT检测细胞的增殖力,细胞黏附实验与transwell法检测细胞的侵袭能力,流式细胞术检测细胞的周期及凋亡率。结果：与生理盐水组比较,中剂量组及高剂量组的抑瘤率分别为（40.26±4.25）%、（44.81±5.74）%,两组比较,差异有统计学意义（P〈0.05）。免疫组织化学显示,中剂量、高剂量姜黄素与吉非替尼联合应用明显抑制c-myc的活化。中剂量、高剂量姜黄素与吉非替尼联合作用SGC-7901细胞后,c-myc表达量明显降低,细胞增殖及侵袭能力明显受到抑制,G0/G1期细胞数明显升高（P〈0.05）,S期细胞数明显降低（P〈0.05）,细胞凋亡率明显高于对照组（P〈0.05）。结论：一定剂量的姜黄素与吉非替尼联合可体内抑制胃癌裸鼠移植瘤的生长及体外抑制SGC-7901细胞的增殖、侵袭能力及促进细胞凋亡,其抑制胃癌生长的机制可能是通过降低c-myc蛋白的表达,从而影响c-myc参与调控的癌细胞增殖,转移过程。

Influence of Curcumin and Gefitinib on SGC-7901 Cell Proliferation of Gastric Cancer and the Growth of Nude Mouse Transplanted Tumor

Objective：To explore the influence of different concentrations of Curcumin combined with Gefitinib on the growth of gastric cancer nude mouse transplanted tumor in vivo and gastric cancer SGC-7901 cell in vitro. Methods：Cell suspension made from SGC-7901 gastric cancer cells were inoculated subcutaneously in nude mice to prepare of nude mice model of gastric carcinoma. The nude mice models were randomly divided into saline group and combination of curcumin and gefitiuib low dose group, middle dose group, high dose group,intraperitoneal injection, once a week. Medication for 4 times, the nude mice were killed, stripping of tumor tissue to weigh quali- ty, calculate tumor inhibition rate. Expression of e-myc was detected by immunohistoehemieal method in tumor tissue. The expression of intracellular c-mye was detected by western blot method, cell proliferation was measured by MTT, cell invasion ability was detected by cell adhesion assay and Transwell method, cell cycle and apoptosis were detected by flow cytometry cell rate in low dose, middle dose, high dose of combination of cureumin and gefitinib groups. Results ： Compared with the normal saline group, the inhibition rate of middle dose group and high dose group were （40.26 ± 4.25 ） % and （ 44.81± 5.74 ） % , and the difference was statistically significant （ P 〈 0. 05 ）. Immunohistochemistry showed that middle dose, high dose of combined application of Curcumin and Gefitinib can significantly inhibit activation of c-mye. After middle dose, high dose of combined application of Cureumin and Gefitinib on SGC-7901 cells, the ex- pression of e-mye significantly decreased, the proliferation and invasion of cells was significantly inhibited, the cell number in G0/G1 phase was increased significantly（ P 〈 0.05 ） , the number of S phase cells decreased significantly（ P 〈 0.05 ） , the apoptosis rate was higher than that of the control group（ P 〈 0.05 ）. Conclusion ： Certain dosage of combination of Curcumin and Gefitinib can inhibit thegrowth of gastric cancer nude mouse transplanted tumor in vitro and SGC-7901 cells proliferation and invasion in vivo, and accelerate apoptosis. Its mechanism may be through reducing the expression of c-myc protein, thus affects the process of c-myc involved regulation of cancer cell proliferation and metastasis.