伊维菌素诱导膀胱癌细胞自噬与凋亡

刘 洋
彭州市人民医院 泌尿外科

摘要

摘要：目的：探究伊维菌素对膀胱癌细胞自噬与凋亡作用。方法：选取两种膀胱癌细胞(EJ-1、5637)与一种膀胱上皮细胞(SV-HUC-1)，采用细胞毒性实验(MTT)证实伊维菌素对膀胱癌和膀胱尿路细胞均有细胞毒性作用；蛋白免疫印迹(WB)检测EJ-1、5637膀胱癌细胞在不同浓度伊维菌素作用下caspase3、caspase9及LC3-II分子表达。结果：不同浓度伊维菌素分别处理三种细胞24h后，MTT检测三种细胞系中存活率均降低，且呈剂量依赖性，但SV-HUC-1细胞中IC50值远高于EJ-1、5637细胞。WB实验显示伊维菌素对两种膀胱癌细胞Cleaved-caspase3、Cleaved-caspase9以及LC3的含量随伊维菌素浓度增加。结论：伊维菌素对膀胱癌细胞具有自噬与凋亡作用。

参考

[1]Bray, F., J. Ferlay, I. Soerjomataram, et al., Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA: a cancer journal for clinicians, 2018. 68(6): p. 394-424.[2]Witjes, J.A., H.M. Bruins, R. Cathomas, et al., European Association of Urology Guidelines on Muscle-invasive and Metastatic Bladder Cancer: Summary of the 2020 Guidelines. Eur Urol, 2020.[3]Hashimoto, H., S.M. Messerli, T. Sudo, et al., Ivermectin inactivates the kinase PAK1 and blocks the PAK1-dependent growth of human ovarian cancer and NF2 tumor cell lines. Drug Discov Ther, 2009. 3(6): p. 243-6.[4]Dou, Q., H.N. Chen, K. Wang, et al., Ivermectin Induces Cytostatic Autophagy by Blocking the PAK1/Akt Axis in Breast Cancer. Cancer Res, 2016. 76(15): p. 4457-69.[5]Levine, B. and G. Kroemer, Biological Functions of Autophagy Genes: A Disease Perspective. Cell, 2019. 176(1-2): p. 11-42.[6]White, E. and R.S. DiPaola, The double-edged sword of autophagy modulation in cancer. Clin Cancer Res, 2009. 15(17): p. 5308-16.[7]Eisenberg-Lerner, A., S. Bialik, H.U. Simon, et al., Life and death partners: apoptosis, autophagy and the cross-talk between them. Cell Death Differ, 2009. 16(7): p. 966-75.[8]陈晓芳, 陈万青, 周薇薇, et al., 2013 年中国膀胱癌发病和死亡流行状况分析. 中国肿瘤, 2018. 27(02): p. 81-85.[9]Jacobs, B.L., C.T. Lee and J.E. Montie, Bladder cancer in 2010: how far have we come? CA Cancer J Clin, 2010. 60(4): p. 244-72.[10]PU, M., B. C and N. BJ, Recurrence, progression and survival in bladder cancer. A retrospective analysis of 232 patients with greater than or equal to 5-year follow-up. Scandinavian journal of urology and nephrology, 1987. 21(3): p. 185-95.[11]高江平 and 金一鹏, 复杂性膀胱癌治疗方式争议与进展. 临床军医杂志, 2017. 45(04): p. 331-333.[12]Konig, I.R., O. Fuchs, G. Hansen, et al., What is precision medicine? Eur Respir J, 2017. 50(4).[13]Deng, L., Y. Lei, R. Liu, et al., Pyrvinium targets autophagy addiction to promote cancer cell death. Cell Death Dis, 2013. 4(5): p. e614.[14]Han, Z., B. Li, J. Wang, et al., Norcantharidin Inhibits SK-N-SH Neuroblastoma Cell Growth by Induction of Autophagy and Apoptosis. Technol Cancer Res Treat, 2017. 16(1): p. 33-44.[15]Maiuri, M.C., E. Zalckvar, A. Kimchi, et al., Self-eating and self-killing: crosstalk between autophagy and apoptosis. Nat Rev Mol Cell Biol, 2007. 8(9): p. 741-52.