sLRIG1与胶质瘤耐药细胞株化疗敏感性的关系

目的 探讨可溶性多亮氨酸重复区免疫球蛋白样蛋白1（sLRIG1）与胶质瘤耐药细胞株化疗敏感性之间的关系。方法 浓度梯度递增法建立多药耐药细胞株U251/VP16；CCK-8法检测sLRIG1对U251细胞的抑制率，确定sLRIG1对U251细胞的最佳作用时间及适宜浓度；CCK-8法检测加入sLRIG1前后三种化疗药（依托泊苷、硫酸长春新碱、替莫唑胺）作用于U251/VP16的抑制率变化。结果 成功建立多药耐药细胞株U251/VP16；sLRIG1对U251细胞的最佳作用时间为30 min，适宜浓度范围为100~200 ng/ml；sLRIG1对U251/VP16的抑制率为（23.76±0.02）%；依托泊苷、硫酸长春新碱、替莫唑胺对U251/VP16的抑制率分别为（9.79±0.08）%、（16.71±0.06）%、（27.14±0.09）%；而在加入sLRIG1后抑制率则分别为（20.34±0.03）%、（31.52±0.07）%、（35.21±0.05）%，加入sLRIG1前后三种化疗药的抑制率差异均有统计学意义（P<0.05）。结论 sLRIG1不仅自身能抑制胶质瘤细胞生长，对耐药胶质瘤细胞的化疗也有增敏作用。

Soluble LRIG1 improves sensitivity of multi-drug resistance glioma cells to chemotherapeutic agents

Objective To investigate the relationship between the soluble leucine-rich repeats and immunoglobulin-like domains 1 (sLRIG1) and the sensitivity of a multi-drug resistance U251 glioma cell line to chemotherapeutic agents. Methods The glioma multiform U251 cells were treated with gradient concentrations of byetoposide (VP16) and finally a multi-drug resistance U251 cell line (U251/VP16) was established by the method of gradient increment of concentration. The inhibitory effects of sLRIG1 on U251 cells and U251/VP16 cells were identified by Cells Counting Kit-8 (CCK-8) in order to determine the optional time and concentration. The sensitivity of U251/VP16 cells to VP16, vincristine sulfate, and temozolomide, VP16+ sLRIG1, vincristine sulfate + sLRIG1, temozolomide + sLRIG1 were also determined by CCK-8. Results A multi-drug resistance U251 cell line (U251/VP16) was successfully established. The optimal time for sLRIG1 inhibiting U251 cells was 30 min and the optimal concentration was 100~200ng/ml. The inhibitory rate of U251/ VP16 cells was (23.76±0.02) % when they were incubated with 200ng/mL of sLRIG1 for 30min. The inhibitory rate of U251/ VP16 were (9.79±0.08) %, (16.71±0.06)%, and (27.14±0.09)% respectively when they were incubated alone with VP16, vincristine sulfate, or temozolomide. The inhibitory rates of U251/ VP16 were (20.34±0.03)%, (31.52±0.07)% and (35.21±0.05)% respectively when they were incubated with VP16 + sLRIG1, vincristine sulfate + sLRIG1 or temozolomide + sLRIG1. The inhibitory rates of U251/ VP16 cells when they were incubated alone with any one of the three agents were significantly lower respectively than those when they were incubated with any one of the three agents and sLRIG1 together (P<0.05). Conclusions The fragment of sLRIG1 is not only capable of inhibiting growth of glioma U251 cells, but it can also play a significant role in enhancing the sensitivity of the multi-drug resistance glioma U251 cells to chemotherapeutic agents in vitro.