组织源性HMGN2对人膀胱移行细胞癌的抗瘤作用研究

Antitumor effect of tissue-derived HMGN2 on human bladder transitional cell carcinoma

目的组织源性高迁移率蛋白N2(HMGN2)对人膀胱移行细胞癌T24细胞及裸鼠移植瘤的抑制肿瘤作用。方法采用高氯酸萃取方法提取组织源性HMGN2。人膀胱移行细胞癌T24细胞与不同浓度(1、3、5μg/mL)的组织源性HMGN2共孵育后,流式细胞术检测T24细胞凋亡的变化;建立裸鼠移植瘤模型,将清洁雄性BALB/c裸鼠30只分为阴性对照组,药物治疗组及阳性对照组,每组10只。分别于瘤体周边注射PBS、HMGN2和顺铂(DDP),20 d后处死裸鼠,检测各组肿瘤质量,HE染色观察瘤组织的坏死情况。结果流式细胞检测结果表明,1、3、5μg/mL HMGN2对T24细胞总凋亡率分别为(17.79±0.53)%、(28.54±0.99)%、(33.92±1.79)%,与阴性对照组(5.95±0.30)%比较,差异具有统计学意义(P<0.0001)。裸鼠移植瘤动物实验中,药物治疗组(0.15±0.01)g与阳性对照组(0.15±0.01)g的肿瘤重量显著小于阴性对照组(0.22±0.01)g,差异具有统计学意义(P<0.05);HE染色结果表明,组织源性HMGN2显著促进了肿瘤细胞的坏死。结论组织源性HMGN2对人膀胱移行细胞癌的抑制肿瘤作用可能与促进肿瘤细胞的凋亡坏死有关。

Objective To explore the inhibitory effect of tissue-derived high mobility protein N2(HMGN2)on human bladder transitional cell carcinoma T24 cells and xenografts in nude mice.Methods The tissuederived HMGN2 was extracted by perchloric acid extraction method.After T24 cells were incubated with different concentrations of tissue-derived HMGN2(1,3,5μg/mL),the apoptosis of T24 cells was detected by flow cytometry.After establishing subcutaneous heterotopic transplanted tumor model,the nude mice were divided into negative control group,drug treatment group and positive control group(10 in each group).PBS,HMGN2 and DDP was respectively injected into the nude mice around the tumor tissue for 20 days.The tumor quality of each group was measured and the necrosis of tumor tissue was observed by HE staining.Results The results of flow cytometry showed that the total apoptosis rate of T24 cells were(17.79±0.53)%,(28.54±0.99)%and(33.92±1.79)%respectively.Compared with the PBS control group(5.95±0.30)%,the difference was statistically significant(P<0.0001).In the nude experiment with transplanted tumor,the tumor weight of the HMGN2 drug treatment group(0.15±0.01)g and DDP positive control group(0.15±0.01)g was significantly smaller than that of negative control group(0.22±0.01)g.The results of HE staining showed that tissue-derived HMGN2 significantly promoted the necrosis of T24 cells.Conclusion The antitumor effect of tissue-derived HMGN2 on bladder cancer may be related to the promotion of apoptosis and necrosis of tumor cells.