放射性^(125)I粒子联合GDC-0941抑制卵巢透明细胞癌生长、提高机体免疫力的实验研究  

Experimental study on radioactive ^(125)I particles combined with GDC-0941 inhibiting the growth of ovarian clear cell carcinoma and improving the body immunity

作　　者：游志鑫[1] 刘爱民[2] 王海东[1] 周莎莎 赵改花[4] 霍红旗[1] YOU Zhixin;LIU Aimin;WANG Haidong;ZHOU Shasha;ZHAO Gaihua;HUO Hongqi(Department of Nuclear Medicine,Handan Central Hospital,Hebei Handan 056001,China;Department of Precision Medicine,Handan Central Hospital,Hebei Handan 056001,China;Second Department of Oncology,Handan Central Hospital,Hebei Handan 056001,China;Department of Medical Record Management,Handan Central Hospital,Hebei Handan 056001,China)

机构地区：[1]邯郸市中心医院核医学科,河北邯郸056001 [2]邯郸市中心医院精准医学科,河北邯郸056001 [3]邯郸市中心医院肿瘤内二科,河北邯郸056001 [4]邯郸市中心医院病案管理科,河北邯郸056001

出　　处：《现代肿瘤医学》2023年第6期1015-1021,共7页Journal of Modern Oncology

基　　金：河北省医学科学研究课题计划项目(编号:20200336)。

摘　　要：目的:探究放射性^(125)I粒子联合Pictilisib(GDC-0941)对卵巢透明细胞癌的杀伤及抗肿瘤免疫效应的影响。方法:将人卵巢透明细胞癌细胞株ES-2分为对照组、^(125)I粒子组(细胞接受^(125)I粒子照射处理)、GDC-0941组(1μmol/L GDC-0941培养细胞24 h)及^(125)I+GDC-0941组(细胞接受^(125)I粒子照射处理,并以1μmol/L GDC-0941培养24 h),按照分组进行处理后,MTT法测定细胞存活率,流式细胞术检测细胞凋亡率,Hoechst 33258染色观察细胞凋亡形态;皮下接种ES-2建立卵巢透明细胞癌裸鼠移植瘤模型,并随机分为对照组、^(125)I粒子组(将^(125)I粒子植入肿瘤组织中心)、GDC-0941组(灌胃125 mg/kg的GDC-0941)及^(125)I+GDC-0941组(将^(125)I粒子植入肿瘤组织中心并灌胃125 mg/kg的GDC-0941),给药开始后,每隔2 d测量并计算肿瘤体积,21 d后处死裸鼠并取其肿瘤组织,电子天平称重,HE染色观察肿瘤组织内细胞生长情况,免疫组织化学染色检测肿瘤组织内凋亡蛋白Cleaved-caspase-3与增殖标记物Ki-67的表达,流式细胞术检测外周血T淋巴细胞亚群。结果:相较于^(125)I粒子照射和GDC-0941单独处理,^(125)I与GDC-0941联合作用下,细胞存活率下降(P<0.05),细胞凋亡率增加(P<0.05),且细胞核浓缩明显,浓染颗粒较多,碎裂现象严重。与^(125)I粒子植入和GDC-0941灌胃的两组裸鼠比较,^(125)I粒子植入联合GDC-0941灌胃的裸鼠,肿瘤生长较为缓慢,肿瘤块变小、质量也减小(P<0.05),肿瘤组织内细胞排列稀疏,Cleaved-caspase-3阳性表达率升高(P<0.05),Ki-67阳性表达率降低(P<0.05),此外,外周血中CD3^(+)CD8^(+)T细胞比例增加。结论:放射性^(125)I粒子联合GDC-0941作用能够显著提高对卵巢透明细胞癌的杀伤作用,且抑制肿瘤生长并改善移植瘤裸鼠的抗肿瘤免疫功能,两者联合作用效果要优于单独作用。Objective:To explore the effect of radioactive^(125)I particles combined with Pictilisib(GDC-0941)on the killing and anti-tumor immune effects of ovarian clear cell carcinoma.Methods:The cultured human ovarian clear cell cancer cell line ES-2 was randomly divided into control group,^(125)I particle group(cells received^(125)I particle irradiation treatment),GDC-0941 group(1μmol/L GDC-0941 cultured cells for 24 h)and^(125)I+GDC-0941 group(cells received^(125)I particle irradiation treatment and cultured at 1μmol/L GDC-0941 for 24 h),after processing according to the grouping,MTT method was used to measure cell survival rate,flow cytometry was used to measure cell apoptosis rate,Hoechst 33258 staining was used to observe cell apoptosis morphology.A nude mouse xenograft model of ovarian clear cell carcinoma was established by subcutaneous inoculation of ES-2.The 16 nude mice that were successfully modeled were randomly divided into a control group,a^(125)I particle group(^(125)I particles were implanted into the tumor tissue center),and a GDC-0941 group(GDC-0941 with 125 mg/kg gavage)and^(125)I+GDC-0941 group(GDC-0941 with^(125)I seeds implanted into the center of tumor tissue and gavage 125 mg/kg GDC-0941),after the administration started,the tumor volume was measured and calculated every 2 days.After 21 days,the nude mice were sacrificed and their tumor tissues were taken,weighed with an electronic balance,HE staining was used to observe the cell growth in the tumor tissues,immunohistochemical staining was used to detect the expression of apoptosis protein Cleaved-caspase-3 and proliferation marker Ki-67 in tumor tissues,flow cytometry was used to detectperipheral blood T lymphocyte subsets.Results:Compared with^(125)I particle irradiation and GDC-0941 treatment alone,the combined effect of^(125)I and GDC-0941 decreased the cell viability(P<0.05)and increased the apoptosis rate(P<0.05).The nuclei were condensed obviously,the densely stained granules were more,and the fragmentation phenomenon was serious.Compared

关 键 词：卵巢透明细胞癌 ^(125)I粒子 GDC-0941 抗肿瘤效应 

分 类 号：R737.31[医药卫生—肿瘤]