顺铂植入剂对人胃癌裸鼠移植瘤中SYK、HER2、CD44V6和PTEN表达的影响

Effect of cisplatin implantation on tumor expression change of SYK, HER2, CD44V6 and PTEN in human gastric carcinoma xenograft of nude mice

目的观察新型顺铂植入剂与常规顺铂注射液在人胃癌裸鼠移植瘤模型中促肿瘤细胞凋亡以及对脾酪氨酸激酶(SYK)、人表皮生长因子受体2(HER2)、黏附分子CD44的变异体6(CD44V6)、与张力蛋白同源的人第10号染色体缺失的磷酸酶基因(PTEN)在胃癌组织中表达水平的影响差异,探讨新型顺铂植入剂在胃癌发生、发展过程中的治疗优势。方法用人胃癌SGC7901细胞株建立BALB/c裸鼠皮下移植瘤模型,随机分3组:PBS瘤内注射组、顺铂瘤内注射组和顺铂植入剂植入组,每组6只。经药物干预后,记录瘤重,计算抑瘤率,并对瘤体进行HE染色,通过免疫组织化学法检测SYK、HER2、PTEN、CD44V6表达水平,流式细胞术检测各组细胞凋亡情况。结果顺铂植入剂能显著抑制移植瘤的生长,促进其凋亡并能较显著提高SYK和PTEN的表达[顺铂植入剂植入组结果均比PBS瘤内注射组、顺铂瘤内注射组高,差异有统计学意义(P<0.05)],降低HER2和CD44V6表达[顺铂植入剂植入组结果均比PBS瘤内注射组、顺铂瘤内注射组低,差异有统计学意义(P<0.05)]。结论顺铂植入剂可能通过下调HER2、CD44V6或上调SYK、PTEN的表达来促进癌细胞的凋亡以发挥抗肿瘤的作用,从而为临床胃癌的治疗提供新思路。

【Objective】 To assess the antitumor effects of cisplatin implants vs common cisplatin injection in a xenograft nude mouse model of human gastric cancer and its effect on the tumor expression change of SYK, HER2, CD44V6 and PTEN against human gastric carcinoma xenograft in nude mice, and to discuss its advantage in the treatment of gastric cancer. 【Methods】 A xenograft nude mouse model of human gastric cancer was established by subcutaneously injecting SGC7901 cells in BALB / c nude mice. The model mice were randomly divided into three groups： A（intratumor injection of PBS）, B（intratumor injection of cisplatin）,and C（cisplatin implantation） with 6 in each group. After drug intervention, tumor weight and volume were calculated. Tumor tissues were observed by HE staining. The protein expressions of spleen tyrosine kinase（SYK）, human epidermal growth factor receptor 2（HER 2）, phosphate and tension homology deleted on chromosome ten（PTEN）, the sixth variant form of adhesion molecule CD44（CD44V6） and cysteinyl aspartate specific protease 3（Caspase 3） / Survivin in tumor tissue were detected by immunohistochemistry. Cell apoptosis was detected by flow cytometry.【Results】 Sustained-release cisplatin significantly promoted apoptosis,suppressed tumor growth, enhanced the expression of SYK and PTEN（that in the group C was higher than those in other groups, P 〈0.05）, reduced the expression of HER 2 and CD44V6（that in the group C was lower than those in other groups, P 〈0.05）. 【Conclusion】 Cisplatin-implants can develop the anticancer function by apoptosis through enhancing the expression of SYK and PTEN, and reducing the expression of HER 2 and CD44V6. It can efficiently kill the tumor, furthermore give new ideas in clinical practice.