Propofol exhibits a tumor‑suppressive effect and regulates cell viability, migration and invasion in bladder carcinoma by targeting the microRNA‑10b/HOXD10 signaling pathway

Qi,Zongcai; Yuan,Lei; Sun,Nenghong

doi:10.3892/ol.2019.10968

Propofol exhibits a tumor‑suppressive effect and regulates cell viability, migration and invasion in bladder carcinoma by targeting the microRNA‑10b/HOXD10 signaling pathway

Authors:
- Zongcai Qi
- Lei Yuan
- Nenghong Sun
View Affiliations

Affiliations: Department of Anesthesiology, Weifang People's Hospital, Weifang, Shandong 261000, P.R. China, Department of Operating Room, The Seventh People's Hospital of Weifang City, Weifang, Shandong 261041, P.R. China
Published online on: October 8, 2019 https://doi.org/10.3892/ol.2019.10968
Pages: 6228-6236

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

2,6‑diisopropylphenol (propofol) is a commonly used intravenous anesthetic drug, which has been reported to serve an antitumor role in human cancers. The current study aimed to assess the effects of propofol on the biological behaviors of human bladder cancer cells and to elucidate its potential molecular mechanism. The results of MTT, wound healing and Matrigel invasion assays demonstrated that propofol significantly inhibited the viability, migration and invasion of bladder cancer T24 cells in vitro. Reverse transcription‑quantitative PCR and western blotting revealed that propofol decreased the expression levels of microRNA (miR)‑10b and increased the expression levels of homeobox D10 (HOXD10) in T24 cells. Luciferase reporter assay revealed that HOXD10 was a direct target of miR‑10b in T24 cells. T24 cells transfected with a miR‑10b mimic significantly reduced the mRNA and protein expression levels of HOXD10. In addition, overexpression of miR‑10b partly reversed the inhibitory effect of propofol on T24 cell viability, migration and invasion induced by upregulation of HOXD10. In summary, the present study focused on the role of propofol in the treatment of bladder cancer and demonstrated that propofol may serve a tumor‑suppressive role and control cell viability, migration and invasion of T24 cells by targeting the miR‑10b/HOXD10 signaling pathway, which indicated that propofol may be used as an effective therapeutic drug for the treatment of bladder cancer.

View Figures

View References

1	Torre LA, Bray F, Siegel RL, Ferlay J, Lortet-Tieulent J and Jemal A: Global cancer statistics, 2012. CA Cancer J Clin. 65:87–108. 2015. View Article : Google Scholar : PubMed/NCBI
2	Zhang Y, Xu F, Zhang FQ, Song L and Chen C: Recent perspectives of bladder cancer diagnostics. Minerva Med. 107:162–166. 2016.PubMed/NCBI
3	Antoni S, Ferlay J, Soerjomataram I, Znaor A, Jemal A and Bray F: Bladder cancer incidence and mortality: A global overview and recent trends. Eur Urol. 71:96–108. 2017. View Article : Google Scholar : PubMed/NCBI
4	Chou R, Selph SS, Buckley DI, Gustafson KS, Griffin JC, Grusing SE and Gore JL: Treatment of muscle-invasive bladder cancer: A systematic review. Cancer. 122:842–851. 2016. View Article : Google Scholar : PubMed/NCBI
5	Siegel RL, Miller KD and Jemal A: Cancer statistics, 2017. CA Cancer J Clin. 67:7–30. 2017. View Article : Google Scholar : PubMed/NCBI
6	Zuiverloon TC and Theodorescu D: Pharmacogenomic considerations in the treatment of muscle-invasive bladder cancer. Pharmacogenomics. 18:1167–1178. 2017. View Article : Google Scholar : PubMed/NCBI
7	Falzone L, Salomone S and Libra M: Evolution of cancer pharmacological treatments at the turn of the third millennium. Front Pharmacol. 9:13002018. View Article : Google Scholar : PubMed/NCBI
8	Lewis BP, Burge CB and Bartel DP: Conserved seed pairing, often flanked by adenosines, indicates that thousands of human genes are microRNA targets. Cell. 120:15–20. 2005. View Article : Google Scholar : PubMed/NCBI
9	Bartel DP: MicroRNAs: Genomics, biogenesis, mechanism, and function. Cell. 116:281–297. 2004. View Article : Google Scholar : PubMed/NCBI
10	Falzone L, Romano GL, Salemi R, Bucolo C, Tomasello B, Lupo G, Anfuso CD, Spandidos DA, Libra M and Candido S: Prognostic significance of deregulated microRNAs in uveal melanomas. Mol Med Rep. 19:2599–2610. 2019.PubMed/NCBI
11	Falzone L, Scola L, Zanghi A, Biondi A, Di Cataldo A, Libra M and Candido S: Integrated analysis of colorectal cancer microRNA datasets: Identification of microRNAs associated with tumor development. Aging (Albany NY). 10:1000–1014. 2018. View Article : Google Scholar : PubMed/NCBI
12	Falzone L, Candido S, Salemi R, Basile MS, Scalisi A, McCubrey JA, Torino F, Signorelli SS, Montella M and Libra M: Computational identification of microRNAs associated to both epithelial to mesenchymal transition and NGAL/MMP-9 pathways in bladder cancer. Oncotarget. 7:72758–72766. 2016. View Article : Google Scholar : PubMed/NCBI
13	Guancial EA, Bellmunt J, Yeh S, Rosenberg JE and Berman DM: The evolving understanding of microRNA in bladder cancer. Urol Oncol. 32:41 e31–40. 2014. View Article : Google Scholar
14	Xiu Y, Liu Z, Xia S, Jin C, Yin H, Zhao W and Wu Q: MicroRNA-137 upregulation increases bladder cancer cell proliferation and invasion by targeting PAQR3. PLoS One. 9:e1097342014. View Article : Google Scholar : PubMed/NCBI
15	Xu T, Qin L, Zhu Z, Wang X, Liu Y, Fan Y, Zhong S, Wang X, Zhang X, Xia L, et al: MicroRNA-31 functions as a tumor suppressor and increases sensitivity to mitomycin-C in urothelial bladder cancer by targeting integrin α5. Oncotarget. 7:27445–27457. 2016.PubMed/NCBI
16	He C, Zhang Q, Gu R, Lou Y and Liu W: miR-96 regulates migration and invasion of bladder cancer through epithelial-mesenchymal transition in response to transforming growth factor-β1. J Cell Biochem. 119:7807–7817. 2018. View Article : Google Scholar : PubMed/NCBI
17	Hertzog JH, Dalton HJ, Anderson BD, Shad AT, Gootenberg JE and Hauser GJ: Prospective evaluation of propofol anesthesia in the pediatric intensive care unit for elective oncology procedures in ambulatory and hospitalized children. Pediatrics. 106:742–747. 2000. View Article : Google Scholar : PubMed/NCBI
18	Altenburg JD, Harvey KA, McCray S, Xu Z and Siddiqui RA: A novel 2,6-diisopropylphenyl-docosahexaenoamide conjugate induces apoptosis in T cell acute lymphoblastic leukemia cell lines. Biochem Biophys Res Commun. 411:427–432. 2011. View Article : Google Scholar : PubMed/NCBI
19	Jiang S, Liu Y, Huang L, Zhang F and Kang R: Effects of propofol on cancer development and chemotherapy: Potential mechanisms. Eur J Pharmacol. 831:46–51. 2018. View Article : Google Scholar : PubMed/NCBI
20	Liu Z, Zhang J, Hong G, Quan J, Zhang L and Yu M: Propofol inhibits growth and invasion of pancreatic cancer cells through regulation of the miR-21/Slug signaling pathway. Am J Transl Res. 8:4120–4133. 2016.PubMed/NCBI
21	Xu J, Xu W and Zhu J: Propofol suppresses proliferation and invasion of glioma cells by upregulating microRNA-218 expression. Mol Med Rep. 12:4815–4820. 2015. View Article : Google Scholar : PubMed/NCBI
22	Schmittgen TD and Livak KJ: Analyzing real-time PCR data by the comparative C(T) method. Nat Protoc. 3:1101–1108. 2008. View Article : Google Scholar : PubMed/NCBI
23	Xiao H, Li H, Yu G, Xiao W, Hu J, Tang K, Zeng J, He W, Zeng G, Ye Z and Xu H: MicroRNA-10b promotes migration and invasion through KLF4 and HOXD10 in human bladder cancer. Oncol Rep. 31:1832–1838. 2014. View Article : Google Scholar : PubMed/NCBI
24	Wang Y, Li Z, Zhao X, Zuo X and Peng Z: miR-10b promotes invasion by targeting HOXD10 in colorectal cancer. Oncol Lett. 12:488–494. 2016. View Article : Google Scholar : PubMed/NCBI
25	Wang YY, Li L, Ye ZY, Zhao ZS and Yan ZL: MicroRNA-10b promotes migration and invasion through Hoxd10 in human gastric cancer. World J Surg Oncol. 13:2592015. View Article : Google Scholar : PubMed/NCBI
26	Cassinello F, Prieto I, del Olmo M, Rivas S and Strichartz GR: Cancer surgery: How may anesthesia influence outcome? J Clin Anesth. 27:262–272. 2015. View Article : Google Scholar : PubMed/NCBI
27	Soltanizadeh S, Degett TH and Gögenur I: Outcomes of cancer surgery after inhalational and intravenous anesthesia: A systematic review. J Clin Anesth. 42:19–25. 2017. View Article : Google Scholar : PubMed/NCBI
28	Wang Z, Kou D, Li Z, He Y, Yu W and Du H: Effects of propofol-dexmedetomidine combination on ischemia reperfusion-induced cerebral injury. NeuroRehabilitation. 35:825–834. 2014.PubMed/NCBI
29	Shin IW, Jang IS, Lee SH, Baik JS, Park KE, Sohn JT, Lee HK and Chung YK: Propofol has delayed myocardial protective effects after a regional ischemia/reperfusion injury in an in vivo rat heart model. Korean J Anesthesiol. 58:378–382. 2010. View Article : Google Scholar : PubMed/NCBI
30	Xu YB, Du QH, Zhang MY, Yun P and He CY: Propofol suppresses proliferation, invasion and angiogenesis by down-regulating ERK-VEGF/MMP-9 signaling in Eca-109 esophageal squamous cell carcinoma cells. Eur Rev Med Pharmacol Sci. 17:2486–2494. 2013.PubMed/NCBI
31	Xu YB, Jiang W, Zhao FR, Li G, Du QH, Zhang MY and Guo XG: Propofol suppresses invasion and induces apoptosis of osteosarcoma cell in vitro via downregulation of TGF-β1 expression. Eur Rev Med Pharmacol Sci. 20:1430–1435. 2016.PubMed/NCBI
32	Wang ZT, Gong HY, Zheng F, Liu DJ and Yue XQ: Propofol suppresses proliferation and invasion of gastric cancer cells via downregulation of microRNA-221 expression. Genet Mol Res. 14:8117–8124. 2015. View Article : Google Scholar : PubMed/NCBI
33	Yu B, Gao W, Zhou H, Miao X, Chang Y, Wang L, Xu M and Ni G: Propofol induces apoptosis of breast cancer cells by downregulation of miR-24 signal pathway. Cancer Biomark. 21:513–519. 2018. View Article : Google Scholar : PubMed/NCBI
34	Sun H and Gao D: Propofol suppresses growth, migration and invasion of A549 cells by down-regulation of miR-372. BMC Cancer. 18:12522018. View Article : Google Scholar : PubMed/NCBI
35	Zhang P, Hong H, Sun X, Jiang H, Ma S, Zhao S, Zhang M, Wang Z, Jiang C and Liu H: MicroRNA-10b regulates epithelial-mesenchymal transition by modulating KLF4/Notch1/E-cadherin in cisplatin-resistant nasopharyngeal carcinoma cells. Am J Cancer Res. 6:141–156. 2016.PubMed/NCBI
36	Bahena-Ocampo I, Espinosa M, Ceballos-Cancino G, Lizarraga F, Campos-Arroyo D, Schwarz A, Maldonado V, Melendez-Zajgla J and Garcia-Lopez P: miR-10b expression in breast cancer stem cells supports self-renewal through negative PTEN regulation and sustained AKT activation. EMBO Rep. 17:648–658. 2016. View Article : Google Scholar : PubMed/NCBI
37	Li Y, Liu J, Fan Y, Fan Y, Li X, Dong M, Liu H and Chen J: Expression levels of microRNA-145 and microRNA-10b are associated with metastasis in non-small cell lung cancer. Cancer Biol Ther. 17:272–279. 2016. View Article : Google Scholar : PubMed/NCBI
38	Zhang L, Sun J, Wang B, Ren JC, Su W and Zhang T: MicroRNA-10b triggers the epithelial-mesenchymal transition (EMT) of laryngeal carcinoma Hep-2 cells by directly targeting the E-cadherin. Appl Biochem Biotechnol. 176:33–44. 2015. View Article : Google Scholar : PubMed/NCBI
39	Sun L, Yan W, Wang Y, Sun G, Luo H, Zhang J, Wang X, You Y, Yang Z and Liu N: MicroRNA-10b induces glioma cell invasion by modulating MMP-14 and uPAR expression via HOXD10. Brain Res. 1389:9–18. 2011. View Article : Google Scholar : PubMed/NCBI
40	Nakayama I, Shibazaki M, Yashima-Abo A, Miura F, Sugiyama T, Masuda T and Maesawa C: Loss of HOXD10 expression induced by upregulation of miR-10b accelerates the migration and invasion activities of ovarian cancer cells. Int J Oncol. 43:63–71. 2013. View Article : Google Scholar : PubMed/NCBI