双PI3K/mTOR抑制剂NVPBEZ235对宫颈癌Hela细胞的放射增敏作用

doi:10.12092/j.issn.1009-2501.2018.01.004

中国临床药理学与治疗学 ›› 2018, Vol. 23 ›› Issue (1): 18-23.doi: 10.12092/j.issn.1009-2501.2018.01.004

双PI3K/mTOR抑制剂NVPBEZ235对宫颈癌Hela细胞的放射增敏作用

郑迎奥¹，李胜泽¹，张雷²，郭祥瑞³，鲍佳茜⁴，吴涛⁴，刘健¹

¹蚌埠医学院第一附属医院肿瘤妇科，²蚌埠医学院第一附属医院肿瘤放疗科，³蚌埠医学院第一附属医院妇产科，蚌埠 233004，安徽；⁴蚌埠医学院生物科学系，蚌埠 233000，安徽

收稿日期:2017-11-13 修回日期:2017-11-29 出版日期:2018-01-26 发布日期:2018-02-07
通讯作者: 刘健，男，硕士，副主任医师，研究方向：妇科肿瘤。 Tel：13966061758 E-mail:elitelj@126.com
作者简介:郑迎奥，女，硕士研究生，研究方向：妇科肿瘤。 Tel：18895602182 E-mail:zya-july@qq.com
基金资助:
安徽省教育厅自然科学基金（KJ2015B041，KJ2015B096）；大学生创业创新项目（19262，201610367002）

Radio sensitizing effect of double PI3K/mTOR inhibitor NVPBEZ235 on Hela cells of cervical cancer

ZHENG Yingao ¹, LI Shengze ¹, ZHANG Lei ², GUO Xiangrui ³, BAO Jiaqian⁴, WU Tao ⁴, LIU Jian ¹

¹ Department of Oncology, the First Affiliated Hospital of Bengbu Medical College, ²Department of Oncology and Radiotherapy, ³Department of Obstetrics and Gynecology, Bengbu 233004, Anhui, China; ⁴ Bengbu Medical College Biological Science Department, Bengbu 233000, Anhui, China

Received:2017-11-13 Revised:2017-11-29 Online:2018-01-26 Published:2018-02-07

摘要/Abstract

摘要：

目的: 探讨双PI3K/mTOR 抑制剂 NVPBEZ235对宫颈癌Hela细胞的放射增敏作用。方法: 四甲基偶氮唑盐（MTT）及集落克隆法测定各因素对Hela细胞的抑制作用。通过流式细胞仪检测药物联合射线（irradiation，IR）对宫颈癌细胞周期的影响。结果: 与对照组相比，NVPBEZ235在体外能够抑制人宫颈癌细胞的生长。NVPBEZ235、IR联合作用细胞，在体外可以使细胞周期阻滞于G2/M期，二者具有协同作用，联合作用效果显著大于单药作用。结论: 20% IC50 NVPBEZ235在体外能够促进细胞对射线照射的敏感性，抑制细胞的增殖从而实现对宫颈癌细胞的放射增敏作用。

关键词: 双PI3K/mTOR抑制剂, NVPBEZ235, Hela, 放射增敏

Abstract:

AIM: To investigate the effect that external irradiation of dual PI3K/mTOR inhibitors NVPBEZ235 on cervical cancer Hela cells. METHODS: Cervical cancer Hela cells treated with different concentrations of NVPBEZ235 and the radiotherapy (irradiation, IR) were examined for cell viability using MTT assay and colony forming ability. The cycle arrest of cervical cancer cells combined drug with IR was analyzed by using the flow cytometry. RESULTS: Compared with the control group, NVPBEZ235 can inhibit human cervical carcinoma cell in vitro (P<0.05). The combined use of NVPBEZ235 significantly enhanced the inhibitory effect of IR (P<0.05) in Hela cells. In vitro, NVPBEZ235 and IR, which had synergistic effect, can block cell cycle to G2/M period by the combined effect which was significantly greater than the effect of one single drug (P<0.05). CONCLUSION: 20% IC50 NVPBEZ235 can promote the cell's radiation sensitivity, inhibit the proliferation of cells, and thereby, increase its radio sensitivity to cervical cancer cells.

Key words: dual PI3K/mTOR inhibitor, NVPBEZ235, Hela, radio sensitization

中图分类号:

R965.2

郑迎奥，李胜泽，张雷，郭祥瑞，鲍佳茜，吴涛，刘健. 双PI3K/mTOR抑制剂NVPBEZ235对宫颈癌Hela细胞的放射增敏作用[J]. 中国临床药理学与治疗学, 2018, 23(1): 18-23.

ZHENG Yingao, LI Shengze, ZHANG Lei, GUO Xiangrui, BAO Jiaqian, WU Tao, LIU Jian. Radio sensitizing effect of double PI3K/mTOR inhibitor NVPBEZ235 on Hela cells of cervical cancer[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2018, 23(1): 18-23.

参考文献

［1］Ferlay J, Shin HR, Bray F, et al. Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008［J］.Int J Cancer,2010,127(12):2893-2917.
［2］Wieringa HW,van der Zee AG,de Vries EG,et al. Breaking the DNA damage response to improve cervical cancer treatment［J］.Cancer Treat Rev,2016,42(3):30-40.
［3］Asimomytis A, Karanikou M, Rodolakis A, et al. mTOR downstream effectors, 4EBP1 and eIF4E, are over expressed and associated with HPV status in precancerous lesions and carcinomas of the uterine cervix ［J］.Oncol Lett,2016,12(5):3234-3240.
［4］Tangjitgamol S, Katanyoo K, Laopaiboon M, et al. Adjuvant chemotherapy after concurrent chemoradiation for locally advanced cervical cancer ［J］.Cochrane Database Syst Rev,2014,3(12):CD010401.
［5］Dizon DS, Mackay HJ, Thomas GM, et al. State of the science in cervical cancer: where we are Today and where we need to go ［J］.Cancer,2014,120(15): 2282-2288.
［6］Musa F,Alard A,David-West G,et al.Dual mTORC1/2 inhibition as a novel strategy for the resensitization and treatment of platinum-resistant ovarian cancer［J］.Mol Cancer Ther,2016,15(7):1557-1567.
［7］Rebecca VW,Massaro RR,Fedorenko IV,et al.Inhibition of autophagy enhances the effects of the AKT inhibitor MK-2206 when combined with paclitaxel and carboplatin in BRAF wild-type melanoma,Pigment［J］.Pigment Cell Melanoma Res,2014,27(3):465-478.
［8］Djuzenova CS, Fiedler V, Katzer A, et al. Dual PI3K- and mTOR-inhibitor PI-103 can either enhance or reduce the radio sensitizing effect of the Hsp90 inhibitor NVP-AUY922 in tumor cells: The role of drug-irradiatio schedule ［J］.Oncotarget,2016,7(25):38191-38209.
［9］Kuger S,Graus D,Brendtke R,et al.Radio sensitization of glioblastoma cell lines by the dual PI3K and mTOR inhibitor NVP-BEZ235 depends on drug-irradiation schedule［J］.Transl Oncol,2013,6(2):169-179.
［10］Liu YN,Wan RZ,Liu ZP，et al.Recent developments of small molecule PI3K/mTOR dual inhibitors［J］.Mini Rev Med Chem,2013,13(14):2047-2059.
［11］Li YC，He SM，He ZX，et al．Plumbagin induces apoptotic and autophagic cell death through inhibition of the PI3K / Akt / m TOR pathway in human non-small cell lung cancer cells ［J］. Cancer Lett, 2014, 344(2):239-259．
［12］Feng T, Zheng L, Liu F, et al. Growth factor progranulin promotes tumorigenesis of cervical cancer via PI3K/Akt/mTOR signaling pathway［J］.Oncotarget, 2016, 7(36):58381-58395.
［13］Maira SM, Stauffer F, Brueggen J, et al. Identification and characterization of NVP-BEZ235, a new orally available dual phosphatidylinositol 3-kinase/mammalian target of rapamycin inhibitor with potent in vivo antitumor activity［J］. Mol Cancer Ther, 2008, 7(7):1851-1863.
［14］Xie G, Wang Z, Chen Y, et al. Dual blocking of PI3K and mTOR signaling by NVP-BEZ235 inhibits proliferation in cervical carcinoma cells and enhances therapeutic response［J］. Cancer Lett, 2017, 1(388):12-20.
［15］Zhao B，Li L，Liu J，et al．Exposure to perfluorooctane sulfonate in utero reduces testosterone production in rat fetal Leydig cells［J］.PLoS One, 2014, 9(1):e78888.
［16］Wang WJ，Long LM，Yang N，et al．NVP-BEZ235，a novel dual PI3K / m TOR inhibitor， enhances the radiosensitivity of human glioma stem cells in vitro［J］. Acta Pharmacol Sin, 2013, 34(5):681-690.

[1]	张哲，吕毓，黄攀豪. NF-κB介导的连翘酯苷B对宫颈癌细胞增殖活性的抑制作用[J]. 中国临床药理学与治疗学, 2020, 25(4): 387-392.
[2]	刘健，崔艳艳，李胜泽，刘红丽，李玉芝，郭苏阳，刘静. 阿司匹林诱导宫颈癌Hela细胞凋亡及抑制增殖的机制研究[J]. 中国临床药理学与治疗学, 2016, 21(11): 1263-1266.
[3]	郑颖. MiR-193b体外协同增强顺铂对宫颈癌细胞的抗肿瘤效应[J]. 中国临床药理学与治疗学, 2015, 20(8): 896-900.
[4]	杨靖亚, 王晓霁, 张建. 羧甲基壳聚糖与阿霉素联合用药的体外抗肿瘤作用[J]. 中国临床药理学与治疗学, 2009, 14(11): 1253-1257.
[5]	王朝霞, 陈意红, 谈文霞, 胡琴, 吉兆宁. 塞来西布对食管癌ECA-109 细胞系放射增敏效应的研究[J]. 中国临床药理学与治疗学, 2009, 14(10): 1095-1100.
[6]	赵令武, 万福生. 白英水提物诱导人宫颈癌HeLa细胞凋亡的实验研究[J]. 中国临床药理学与治疗学, 2007, 12(8): 883-887.
[7]	马润娣, 于立坚, 苏伟明, 邵海艳, 廖铭能, 何冬梅, 黄来珍. 土贝母苷甲诱导HeLa 细胞周期阻滞和凋亡[J]. 中国临床药理学与治疗学, 2004, 9(3): 261-269.
[8]	张晶, 杨静, 吴基良, 张琳, 詹春. 异甘草素脂质体的制备及其对宫颈癌细胞体外增殖的抑制作用[J]. 中国临床药理学与治疗学, 2004, 9(11): 1268-1272.
[9]	霍冠华, 吕耀凤, 张金凤, 高洪秋. 碱性彗星试验检测γ-射线照射与维生素K3联合应用对人宫颈癌HeLa细胞的细胞毒性影响[J]. 中国临床药理学与治疗学, 2003, 8(5): 530-533.

双PI3K/mTOR抑制剂NVPBEZ235对宫颈癌Hela细胞的放射增敏作用

Radio sensitizing effect of double PI3K/mTOR inhibitor NVPBEZ235 on Hela cells of cervical cancer

PDF (PC)

可视化

摘要/Abstract

引用本文

使用本文

参考文献

相关文章 9

编辑推荐

Metrics

本文评价