Sufentanil impairs autophagic degradation and inhibits cell migration in NCI‑H460 in vitro

Jiang,Hui; Wang,Hongxian; Zou,Weiwei; Hu,Yuexia; Chen,Chen; Wang,Chunhui

doi:10.3892/ol.2019.10997

Sufentanil impairs autophagic degradation and inhibits cell migration in NCI‑H460 in vitro

Authors:
- Hui Jiang
- Hongxian Wang
- Weiwei Zou
- Yuexia Hu
- Chen Chen
- Chunhui Wang
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Affiliations: Department of Anesthesiology, The Fourth Affiliated Hospital of Anhui Medical University, Anhui, Hefei 20032, P.R. China
Published online on: October 17, 2019 https://doi.org/10.3892/ol.2019.10997
Pages: 6829-6835
Copyright: © Jiang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Metastasis, which involves the spread of cancer cells to distant tissues and organs, is a major cause of cancer‑associated mortality. Although the use of anesthetics and analgesics may affect cancer cell metastasis, the underlying molecular mechanism remains unclear. Autophagy is a lysosome‑based dynamic intracellular catabolic process that serves a crucial role in cancer cell metastasis. In order to investigate the role of autophagy in the migration of cancer cells treated with analgesics, immunofluorescence, western blotting, wound healing assay and cell invasion assay were performed in the present study. The results from immunofluorescence and western blotting demonstrated that the opioid analgesic sufentanil stimulated LC3 induction in NCI‑H460 cells. Furthermore, sufentanil increased LC3 and Beclin1 protein levels, but inhibited the fusion of autophagosomes and lysosomes. In addition, sufentanil decreased cathepsin D protein level and increased p62 protein level. The addition of chloroquine (CQ) to sufentanil did not induce a further increase in LC3‑II protein levels in NCI‑H460 cells, suggesting the impairment of autophagic degradation. Furthermore, treatment with trehalose stimulated the migration of sufentanil‑treated cells, whereas additional treatment with CQ did not further decrease the migration of sufentanil‑treated cells. In addition, sufentanil co‑treatment with trehalose significantly increased the invasion of lung cancer cells, whereas, additional treatment with CQ did not further reduce the invasion of sufentanil‑treated cells. These results indicated that autophagy may be involved in the inhibition of NCI‑H460 cell migration by sufentanil, and that sufentanil may be considered as a favorable analgesic for patients with lung cancer.

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1	Bray F, Jemal A, Grey N, Ferlay J and Forman D: Global cancer transitions according to the human development index (2008–2030): A population-based study. Lancet Oncol. 13:790–801. 2012. View Article : Google Scholar : PubMed/NCBI
2	Park CG, Hartl CA, Schmid D, Carmona EM, Kim HJ and Goldberg MS: Extended release of perioperative immunotherapy prevents tumor recurrence and eliminates metastases. Sci Transl Med. 10(pii): eaar19162018. View Article : Google Scholar : PubMed/NCBI
3	Moody SE, Perez D, Pan TC, Sarkisian CJ, Portocarrero CP, Sterner CJ, Notorfrancesco KL, Cardiff RD and Chodosh LA: The transcriptional repressor Snail promotes mammary tumor recurrence. Cancer Cell. 8:197–209. 2005. View Article : Google Scholar : PubMed/NCBI
4	Sessler DI: Long-term consequences of anesthetic management. Anesthesiology. 111:1–4. 2009. View Article : Google Scholar : PubMed/NCBI
5	Snyder GL and Greenberg S: Effect of anaesthetic technique and other perioperative factors on cancer recurrence. Br J Anaesthesia. 105:106–115. 2010. View Article : Google Scholar
6	Boland JW and Pockley AG: Influence of opioids on immune function in patients with cancer pain: From bench to bedside. Br J Pharmacol. 175:2726–2736. 2018. View Article : Google Scholar : PubMed/NCBI
7	Le Gac G, Angenard G, Clement B, Laviolle B, Coulouarn C and Beloeil H: Local anesthetics inhibit the growth of human hepatocellular carcinoma cells. Anesth Anal. 125:1600–1609. 2017. View Article : Google Scholar
8	Xuan W, Zhao H, Hankin J, Chen L, Yao S and Ma D: Local anesthetic bupivacaine induced ovarian and prostate cancer apoptotic cell death and underlying mechanisms in vitro. Sci Rep. 6:262772016. View Article : Google Scholar : PubMed/NCBI
9	Chen X, Wu Q, You L, Chen S, Zhu M and Miao C: Propofol attenuates pancreatic cancer malignant potential via inhibition of NMDA receptor. Eur J Pharmacol. 795:150–159. 2017. View Article : Google Scholar : PubMed/NCBI
10	Mishra SK, Kang JH, Lee CW, Oh SH, Ryu JS, Bae YS and Kim HM: Midazolam induces cellular apoptosis in human cancer cells and inhibits tumor growth in xenograft mice. Mol Cells. 36:219–226. 2013. View Article : Google Scholar : PubMed/NCBI
11	Huang H, Benzonana LL, Zhao H, Watts HR, Perry NJ, Bevan C, Brown R and Ma D: Prostate cancer cell malignancy via modulation of HIF-1α pathway with isoflurane and propofol alone and in combination. Br J Cancer. 111:1338–1349. 2014. View Article : Google Scholar : PubMed/NCBI
12	Benzonana LL, Perry NJ, Watts HR, Yang B, Perry IA, Coombes C, Takata M and Ma D: Isoflurane, a commonly used volatile anesthetic, enhances renal cancer growth and malignant potential via the hypoxia-inducible factor cellular signaling pathway in vitro. Anesthesiology. 119:593–605. 2013. View Article : Google Scholar : PubMed/NCBI
13	Kenific CM, Thorburn A and Debnath J: Autophagy and metastasis: Another double-edged sword. Curr Opin Cell Biol. 22:241–245. 2010. View Article : Google Scholar : PubMed/NCBI
14	Xie Z and Klionsky DJ: Autophagosome formation: Core machinery and adaptations. Nat Cell Biol. 9:1102–1109. 2007. View Article : Google Scholar : PubMed/NCBI
15	Li R, Ma H, Zhang X, Li C, Xiong J, Lu T, Mao Y, Dai J, Liu L and Ding Z: Impaired autophagosome clearance contributes to local anesthetic bupivacaine-induced myotoxicity in mouse myoblasts. Anesthesiology. 122:595–605. 2015. View Article : Google Scholar : PubMed/NCBI
16	Zhang X, Zhou Y, Xu M and Chen G: Autophagy is involved in the sevoflurane anesthesia-induced cognitive dysfunction of aged rats. PLoS One. 11:e01535052016. View Article : Google Scholar : PubMed/NCBI
17	Su LY, Luo R, Liu Q, Su JR, Yang LX, Ding YQ, Xu L and Yao YG: Atg5- and Atg7-dependent autophagy in dopaminergic neurons regulates cellular and behavioral responses to morphine. Autophagy. 13:1496–1511. 2017. View Article : Google Scholar : PubMed/NCBI
18	Chen X, Li LY, Jiang JL, Li K, Su ZB, Zhang FQ, Zhang WJ and Zhao GQ: Propofol elicits autophagy via endoplasmic reticulum stress and calcium exchange in C2C12 myoblast cell line. PLoS One. 13:e01979342018. View Article : Google Scholar : PubMed/NCBI
19	Zhou YF, Wang QX, Zhou HY and Chen G: Autophagy activation prevents sevoflurane-induced neurotoxicity in H4 human neuroglioma cells. Acta Pharmacol Sin. 37:580–588. 2016. View Article : Google Scholar : PubMed/NCBI
20	Yao J, Ma C, Gao W, Liang J, Liu C, Yang H, Yan Q and Wen Q: Fentanyl induces autophagy via activation of the ROS/MAPK pathway and reduces the sensitivity of cisplatin in lung cancer cells. Oncol Rep. 36:3363–3370. 2016. View Article : Google Scholar : PubMed/NCBI
21	Wei PF, Jin PP, Barui AK, Hu Y, Zhang L, Zhang JQ, Shi SS, Zhang HR, Lin J, Zhou W, et al: Differential ERK activation during autophagy induced by europium hydroxide nanorods and trehalose: Maximum clearance of huntingtin aggregates through combined treatment. Biomaterials. 73:160–174. 2015. View Article : Google Scholar : PubMed/NCBI
22	Bundscherer A, Malsy M, Gebhardt K, Metterlein T, Plank C, Wiese CH, Gruber M and Graf BM: Effects of ropivacaine, bupivacaine and sufentanil in colon and pancreatic cancer cells in vitro. Pharmacol Res. 95-96:126–131. 2015. View Article : Google Scholar : PubMed/NCBI
23	Ni HM, Bockus A, Wozniak AL, Jones K, Weinman S, Yin XM and Ding WX: Dissecting the dynamic turnover of GFP-LC3 in the autolysosome. Autophagy. 7:188–204. 2011. View Article : Google Scholar : PubMed/NCBI
24	Margariti A, Li H, Chen T, Martin D, Vizcay-Barrena G, Alam S, Karamariti E, Xiao Q, Zampetaki A, Zhang Z, et al: XBP1 mRNA splicing triggers an autophagic response in endothelial cells through BECLIN-1 transcriptional activation. J Biol Chem. 288:859–872. 2013. View Article : Google Scholar : PubMed/NCBI
25	Yu L, McPhee CK, Zheng L, Mardones GA, Rong Y, Peng J, Mi N, Zhao Y, Liu Z, Wan F, et al: Termination of autophagy and reformation of lysosomes regulated by mTOR. Nature. 465:942–946. 2010. View Article : Google Scholar : PubMed/NCBI
26	Bjorkoy G, Lamark T, Brech A, Outzen H, Perander M, Overvatn A, Stenmark H and Johansen T: p62/SQSTM1 forms protein aggregates degraded by autophagy and has a protective effect on huntingtin-induced cell death. J Cell Biol. 171:603–614. 2005. View Article : Google Scholar : PubMed/NCBI
27	Bjorkoy G, Lamark T, Pankiv S, Overvatn A, Brech A and Johansen T: Monitoring autophagic degradation of p62/SQSTM1. Methods Enzymol. 452:181–197. 2009. View Article : Google Scholar : PubMed/NCBI
28	Pellegrini P, Strambi A, Zipoli C, Hägg-Olofsson M, Buoncervello M, Linder S and De Milito A: Acidic extracellular pH neutralizes the autophagy-inhibiting activity of chloroquine: Implications for cancer therapies. Autophagy. 10:562–571. 2014. View Article : Google Scholar : PubMed/NCBI
29	Zhang J, Dai W, Geng P, Zhang L, Tan Q, Cheng D, Wei P, Yang Z, Zhang L, Gu E, et al: Midazolam enhances mutant huntingtin protein accumulation via impairment of autophagic degradation in vitro. Cell Physiol Biochem. 48:683–691. 2018. View Article : Google Scholar : PubMed/NCBI
30	Connolly C and Buggy DJ: Opioids and tumour metastasis: Does the choice of the anesthetic-analgesic technique influence outcome after cancer surgery? Curr Opin Anaesthesiol. 29:468–474. 2016. View Article : Google Scholar : PubMed/NCBI
31	Gach K, Szemraj J, Wyrebska A and Janecka A: The influence of opioids on matrix metalloproteinase-2 and −9 secretion and mRNA levels in MCF-7 breast cancer cell line. Mol Biol Rep. 38:1231–1236. 2011. View Article : Google Scholar : PubMed/NCBI
32	Bimonte S, Barbieri A, Palma G and Arra C: The role of morphine in animal models of human cancer: Does morphine promote or inhibit the tumor growth? Biomed Res Int. 2013:2581412013. View Article : Google Scholar : PubMed/NCBI
33	Biki B, Mascha E, Moriarty DC, Fitzpatrick JM, Sessler DI and Buggy DJ: Anesthetic technique for radical prostatectomy surgery affects cancer recurrence: A retrospective analysis. Anesthesiology. 109:180–187. 2008. View Article : Google Scholar : PubMed/NCBI
34	Christopherson R, James KE, Tableman M, Marshall P and Johnson FE: Long-term survival after colon cancer surgery: A variation associated with choice of anesthesia. Anesth Analg. 107:325–332. 2008. View Article : Google Scholar : PubMed/NCBI
35	Tedore T: Regional anaesthesia and analgesia: Relationship to cancer recurrence and survival. Br J Anaesth. 115 (Suppl 2):ii34–ii45. 2015. View Article : Google Scholar : PubMed/NCBI
36	Page GG, Blakely WP and Ben-Eliyahu S: Evidence that postoperative pain is a mediator of the tumor-promoting effects of surgery in rats. Pain. 90:191–199. 2001. View Article : Google Scholar : PubMed/NCBI
37	Saurer TB, Ijames SG, Carrigan KA and Lysle DT: Neuroimmune mechanisms of opioid-mediated conditioned immunomodulation. Brain Behav Immun. 22:89–97. 2008. View Article : Google Scholar : PubMed/NCBI
38	Gong L, Qin Q, Zhou L, Ouyang W and Li Y, Wu Y and Li Y: Effects of fentanyl anesthesia and sufentanil anesthesia on regulatory T cells frequencies. Int J Clin Exp Pathol. 7:7708–7716. 2014.PubMed/NCBI