|Table of Contents|

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

Journal Of Modern Oncology[ISSN:1672-4992/CN:61-1415/R]

Issue:
2023 06
Page:
1015-1021
Research Field:
Publishing date:

Info

Title:
Experimental study on radioactive 125I particles combined with GDC-0941 inhibiting the growth of ovarian clear cell carcinoma and improving the body immunity
Author(s):
YOU Zhixin1; LIU Aimin2; WANG Haidong1; ZHOU Shasha3; ZHAO Gaihua4; HUO Hongqi1
1.Department of Nuclear Medicine;2.Department of Precision Medicine;3.Second Department of Oncology;4.Department of Medical Record Management,Handan Central Hospital,Hebei Handan 056001，China.
Keywords:
ovarian clear cell carcinoma; 125I particles; GDC-0941; anti-tumor effect
PACS:
R737.31
DOI:
10.3969/j.issn.1672-4992.2023.06.006
Abstract:
Objective:To explore the effect of radioactive 125I 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,125I particle group (cells received 125I particle irradiation treatment),GDC-0941 group (1 μmol/L GDC-0941 cultured cells for 24 h) and 125I+GDC-0941 group (cells received 125I particle irradiation treatment and cultured at 1 μmol/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 125I particle group (125I particles were implanted into the tumor tissue center),and a GDC-0941 group (GDC-0941 with 125 mg/kg gavage) and 125I+GDC-0941 group (GDC-0941 with 125I 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 125I particle irradiation and GDC-0941 treatment alone,the combined effect of 125I 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 with the two groups of nude mice implanted with 125I seeds and gavaged with GDC-0941,the nude mice implanted with 125I seeds and gavaged with GDC-0941 had slower tumor growth,smaller tumor mass and reduced mass (P<0.05),the cells in the tumor tissue were sparsely arranged,the positive expression rate of Cleaved-caspase-3 was increased(P<0.05),and the positive expression rate of Ki-67 was decreased (P<0.05).In addition,the proportion of CD3+CD8+T cells in peripheral blood increased (P<0.05).Conclusion:The combination of radioactive 125I particles and GDC-0941 can significantly increase the killing effect on ovarian clear cell carcinoma,inhibit tumor growth and improve the anti-tumor immune function of transplanted tumor nude mice.The combined effect of the two is better than the single effect.

References:

［1］ ZHU C,XU Z,ZHANG T,et al.Updates of pathogenesis,diagnostic and therapeutic perspectives for ovarian clear cell carcinoma［J］.J Cancer,2021,12(8):2295-2316.
［2］ ODA K,HAMANISHI J,MATSUO K,et al.Genomics to immunotherapy of ovarian clear cell carcinoma:Unique opportunities for management［J］.Gynecol Oncol,2018,151(2):381-389.
［3］ LE SAUX O,RAY-COQUARD I,LABIDI-GALY SI.Challenges for immunotherapy for the treatment of platinum resistant ovarian cancer［J］.Semin Cancer Biol,2020,12:S1044-579X(20)30193-0.
［4］ TATE S,NISHIKIMI K,MATSUOKA A,et al.Bevacizumab in first-line chemotherapy improves progression-free survival for advanced ovarian clear cell carcinoma［J］.Cancers (Basel),2021,13(13):3177.
［5］ JIANG L,WAN C,GUO Q,et al.Efficacy of 125I seed implantation combined with intermittent hormonal therapy on moderate- and high-risk non-metastatic prostate cancer［J］.J BUON,2020,25(6):2616-2622.
［6］ YANG DY,LIN YP,XUE C,et al.CT-guided percutaneous implantation of 125I particles in treatment of early lung cancer［J］.J Thorac Dis,2020,12(10):5996-6009.
［7］ SONG Z,GUO X,YIN C,et al.Therapeutic efficacy of TACE 125I seed implantation and its combination with intra-tumor injection of cisplatin for the treatment of hepatocellular carcinoma［J］.Indian J Cancer,2021,58(1):57-61.
［8］ 徐学勋,肖琳.放射性125I粒子组织间植入治疗复发性卵巢癌的研究进展［J］.世界最新医学信息文摘,2019,19(30):147-148. XU XX,XIAO L.Research progress of radioactive 125I seed interstitial implantation in the treatment of recurrent ovarian cancer［J］.World Latest Medicine Information,2019,19(30):147-148.
［9］ 周辉.CT引导下肿瘤组织间125I粒子植入术联合乌鸡白凤丸对卵巢癌术后复发患者中位生存期及毒副反应的影响［J］.现代医用影像学,2018,27(03):987-988. ZHOU H.Effects of CT-guided inter-tumor 125I seed implantation combined with Wuji Baifeng Pills on median survival and toxic and side effects of ovarian cancer patients with postoperative recurrence［J］.Modern Medical Imageology,2018,27(03):987-988.
［10］ EHRHARDT M,CRAVEIRO RB,VELZ J,et al.The FDA approved PI3K inhibitor GDC-0941 enhances in vitro the anti-neoplastic efficacy of Axitinib against c-myc-amplified high-risk medulloblastoma［J］.J Cell Mol Med,2018,22(4):2153-2161.
［11］ HUANG TT,LAMPERT EJ,COOTS C,et al.Targeting the PI3K pathway and DNA damage response as a therapeutic strategy in ovarian cancer［J］.Cancer Treat Rev,2020,86:102021.
［12］ 次旦旺久,畅智慧,赵相轩,等.125I放射性粒子持续照射抑制HepG2肝癌细胞增殖的作用机制［J］.临床肝胆病杂志,2016,32(10):1920-1924. CIDAN WJ,CHANG ZH,ZHAO XX,et al.Effect of continuous irradiation with 125I radioactive seeds in inhibiting HepG2 cell proliferation and related mechanisms［J］.Journal of Clinical Hepatology,2016,32(10):1920-1924.
［13］ 朱中博,钱建升,杨硕,等.不同剂量125I粒子植入对人乳腺癌裸鼠荷瘤增殖的抑制作用及其机制［J］.吉林大学学报(医学版),2019,45(06):1305-1309. ZHU ZB,QIAN JS,YANG S,et al.Inhibitory effect of difference doses of 125I seed Implantation on tumor-bearing proliferation in nude mice with breast cancer and its mechanics［J］.Journal of Jilin University(Medicine Edition),2019,45(06):1305-1309.
［14］ KIM J,PARK EY,KIM O,et al.Cell origins of high-grade serous ovarian cancer［J］.Cancers (Basel),2018,10(11):433.
［15］ ELVIN JA,CHURA J,GAY LM,et al.Comprehensive genomic profiling (CGP) of ovarian clear cell carcinomas (OCCC) identifies clinically relevant genomic alterations (CRGA) and targeted therapy options［J］.Gynecol Oncol Rep,2017,20:62-66.
［16］ CHEN E,ZHANG Y,ZHANG H,et al.Dosimetry study of three-dimensional print template for 125I implantation therapy［J］.Radiat Oncol,2021,16(1):115.
［17］ TANAKA K,KAJIMOTO T,HAYASHI T,et al.An in vitro verification of strength estimation for moving an 125I source during implantation in brachytherapy［J］.J Radiat Res,2018,59(4):484-489.
［18］ LUO M,CHEN J,ZHONG Z,et al.CT-guided 125I brachytherapy combined with chemotherapy for the treatment of unresectable or locally advanced pancreatic carcinoma［J］.Diagn Interv Radiol,2021,27(1):50-58.
［19］ ZENG Y,MAO Y,SHI Z,et al.Observation of therapeutic effect of 125I seed implantation combined with chemotherapy and antiviral therapy on HBV-related liver cancer［J］.J BUON,2019,24(4):1414-1419.
［20］ 曹熠熠,李文波,翁宇,等. 125I粒子植入联合抗PD-1治疗对小鼠Lewis肺癌的抑制作用研究［J］.中国肿瘤临床,2021,48(05):225-229. CAO YY,LI WB,WENG Y,et al.Effect of iodine-125 particle implantation combined with anti-PD-1 therapy on Lewislung cancer in mice［J］.Chinese Journal of Clinical Oncology,2021,48(05):225-229.
［21］ JUNTTILA TT,AKITA RW,PARSONS K,et al.Ligand-independent HER2/HER3/PI3K complex is disrupted by trastuzumab and is effectively inhibited by the PI3K inhibitor GDC-0941［J］.Cancer Cell，2009,15(5):429-440.
［22］ GARCIA-MARTINEZ JM,WULLSCHLEGER S,PRESTON G,et al.Effect of PI3K- and mTOR-specific inhibitors on spontaneous B-cell follicular lymphomas in PTEN/LKB1-deficient mice［J］.Br J Cancer,2011,104(7):1116-1125.
［23］ VESELY MD,KERSHAW MH,SCHREIBER RD,et al.Natural innate and adaptive immunity to cancer［J］.Annu Rev Immunol,2011,29:235-271.
［24］ CHEN DS,MELLMAN I.Oncology meets immunology:the cancer-immunity cycle［J］.Immunity,2013,39(1):1-10.

Memo

Memo:
河北省医学科学研究课题计划项目(编号：20200336)
Last Update: 1900-01-01