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Anti-Cancer Agents in Medicinal Chemistry

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ISSN (Print): 1871-5206
ISSN (Online): 1875-5992

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Research Article

Propofol and Sevoflurane Alleviate Malignant Biological Behavior and Cisplatin Resistance of Xuanwei Lung Adenocarcinoma by Modulating the Wnt/β-catenin Pathway and PI3K/AKT Pathway

Author(s): Yuhang Quan, Shanshan Li, Yahong Wang, Guangshun Liu, Zhiyong Lv and Zhonghui Wang*

Volume 22, Issue 11, 2022

Published on: 21 December, 2021

Page: [2098 - 2108] Pages: 11

DOI: 10.2174/1871520621666211026092405

open access plus

Abstract

Background: Recent studies have shown that propofol and sevoflurane, two common anesthetics, can prevent tumor development. The prevalence of lung adenocarcinoma in China is highest in Yunnan Xuanwei, and many patients with lung cancer in this area are often resistant to platinum-based treatments.

Objective: The objective of the study was to investigate the effects of propofol and sevoflurane on malignant biological behavior and cisplatin resistance of Xuanwei lung adenocarcinoma.

Methods: Herein, XWLC-05/R, a cisplatin-resistant cell line of XWLC-05 cells from Xuanwei lung adenocarcinoma, was constructed. The XWLC-05 cells and XWLC-05/R cells were treated with propofol and sevoflurane singly or as a combination and subjected to CCK-8 assay, clone formation tests, and flow cytometry analysis to assess the proliferation level of cells. The morphology and number of apoptotic bodies in XWLC-05 cells and XWLC-05/R were examined with a transmission electron microscope. The ANNEXIN V-FITC/PI and transwell assays were performed to evaluate apoptosis, invasion, and migration of the cells. Subsequently, we constructed a Xuanwei lung adenocarcinoma xenograft model to investigate the effects of propofol and sevoflurane on the tumorigenicity of XWLC-05 cells in vivo.

Results: Treatment with propofol and sevoflurane significantly inhibited proliferation, invasion, migration, and induced apoptosis of XWLC-05 and XWLC-05/R cells. These effects were more pronounced when propofol and sevoflurane were co-incubated with the cells. Moreover, both propofol and sevoflurane significantly inhibited Wnt/β- catenin and PI3K/AKT pathways. Moreover, the two drugs effects suppressed the malignant biological behavior of XWLC-05 cells and XWLC-05/R cells, and this effect was counteracted by 740Y-P (PI3K/AKT pathway activator) and Wnt pathway activator 1 (Wnt/β-catenin pathway activator). In vivo experiments confirmed that propofol and sevoflurane alleviated the tumorigenicity of XWLC-05 cells.

Conclusions: In summary, this study shows, for the first time, that propofol and sevoflurane decrease the proliferation, invasion, migration and induce apoptosis of XWLC-05 cells and XWLC-05/R cells by impeding the Wnt/β-catenin and PI3K/AKT signaling pathways, thereby alleviating the development of Xuanwei lung adenocarcinoma in vivo. Moreover, these effects are more pronounced when the two drugs are combined.

Keywords: Propofol, sevoflurane, Wnt/β-catenin pathway, PI3K/AKT pathway, Xuanwei lung adenocarcinoma, malignant biological behavior, cisplatin resistance

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[1]
Gridelli, C.; Rossi, A.; Carbone, D.P.; Guarize, J.; Karachaliou, N.; Mok, T.; Petrella, F.; Spaggiari, L.; Rosell, R. Non-small-cell lung cancer. Nat. Rev. Dis. Primers, 2015, 1, 15009.
[http://dx.doi.org/10.1038/nrdp.2015.9] [PMID: 27188576]
[2]
Torre, L.A.; Bray, F.; Siegel, R.L.; Ferlay, J.; Lortet-Tieulent, J.; Jemal, A. Global cancer statistics, 2012. CA Cancer J. Clin., 2015, 65(2), 87-108.
[http://dx.doi.org/10.3322/caac.21262] [PMID: 25651787]
[3]
Smith, R.A.; Andrews, K.S.; Brooks, D.; Fedewa, S.A.; Manassaram-Baptiste, D.; Saslow, D.; Brawley, O.W.; Wender, R.C. Cancer screening in the United States, 2018: A review of current American Cancer Society guidelines and current issues in cancer screening. CA Cancer J. Clin., 2018, 68(4), 297-316.
[http://dx.doi.org/10.3322/caac.21446] [PMID: 29846940]
[4]
Wang, X.; Li, J.; Duan, Y.; Wu, H.; Xu, Q.; Zhang, Y. Whole genome sequencing analysis of lung adenocarcinoma in Xuanwei, China. Thorac. Cancer, 2017, 8(2), 88-96.
[http://dx.doi.org/10.1111/1759-7714.12411] [PMID: 28083984]
[5]
Xiao, Y.; Shao, Y.; Yu, X.; Zhou, G. The epidemic status and risk factors of lung cancer in Xuanwei City, Yunnan Province, China. Front. Med., 2012, 6(4), 388-394.
[http://dx.doi.org/10.1007/s11684-012-0233-3] [PMID: 23224416]
[6]
Lin, H.; Ning, B.; Li, J.; Zhao, G.; Huang, Y.; Tian, L. Temporal trend of mortality from major cancers in Xuanwei, China. Front. Med., 2015, 9(4), 487-495.
[http://dx.doi.org/10.1007/s11684-015-0413-z] [PMID: 26303302]
[7]
Cao, Y.; Gao, H. Prevalence and causes of air pollution and lung cancer in Xuanwei City and Fuyuan County, Yunnan Province, China. Front. Med., 2012, 6(2), 217-220.
[http://dx.doi.org/10.1007/s11684-012-0192-8] [PMID: 22573219]
[8]
Downward, G.S.; Hu, W.; Large, D.; Veld, H.; Xu, J.; Reiss, B.; Wu, G.; Wei, F.; Chapman, R.S.; Rothman, N.; Qing, L.; Vermeulen, R. Heterogeneity in coal composition and implications for lung cancer risk in Xuanwei and Fuyuan counties, China. Environ. Int., 2014, 68, 94-104.
[http://dx.doi.org/10.1016/j.envint.2014.03.019] [PMID: 24721117]
[9]
Seow, W. J.; Hu, W.; Vermeulen, R.; Hosgood, H. D., III; Downward, G. S.; Chapman, R. S.; He, X.; Bassig, B. A.; Kim, C.; Wen, C.J.C.J.O.C. Household air pollution and lung cancer in China: A review of studies in Xuanwei. 2014, 33(10), 471.
[http://dx.doi.org/10.5732/cjc.014.10132]
[10]
Ho, K.F.; Chang, C.C.; Tian, L.; Chan, C.S.; Musa Bandowe, B.A.; Lui, K.H.; Lee, K.Y.; Chuang, K.J.; Liu, C.Y.; Ning, Z.; Chuang, H.C. Effects of polycyclic aromatic compounds in fine particulate matter generated from household coal combustion on response to EGFR mutations in vitro. Environmental pollution (Barking, Essex : 1987), 2016, 218, 1262-1269.
[11]
Kelland, L. The resurgence of platinum-based cancer chemotherapy. Nat. Rev. Cancer, 2007, 7(8), 573-584.
[http://dx.doi.org/10.1038/nrc2167] [PMID: 17625587]
[12]
Browning, R.J.; Reardon, P.J.T.; Parhizkar, M.; Pedley, R.B.; Edirisinghe, M.; Knowles, J.C.; Stride, E. Drug delivery strategies for platinum-based chemotherapy. ACS Nano, 2017, 11(9), 8560-8578.
[http://dx.doi.org/10.1021/acsnano.7b04092] [PMID: 28829568]
[13]
Fisher, D.E. Apoptosis in cancer therapy: Crossing the threshold. Cell, 1994, 78(4), 539-542.
[http://dx.doi.org/10.1016/0092-8674(94)90518-5] [PMID: 8069905]
[14]
Dasari, S.; Tchounwou, P.B. Cisplatin in cancer therapy: Molecular mechanisms of action. Eur. J. Pharmacol., 2014, 740, 364-378.
[http://dx.doi.org/10.1016/j.ejphar.2014.07.025] [PMID: 25058905]
[15]
Galluzzi, L.; Senovilla, L.; Vitale, I.; Michels, J.; Martins, I.; Kepp, O.; Castedo, M.; Kroemer, G. Molecular mechanisms of cisplatin resistance. Oncogene, 2012, 31(15), 1869-1883.
[http://dx.doi.org/10.1038/onc.2011.384] [PMID: 21892204]
[16]
Shen, D.W.; Pouliot, L.M.; Hall, M.D.; Gottesman, M.M. Cisplatin resistance: A cellular self-defense mechanism resulting from multiple epigenetic and genetic changes. Pharmacol. Rev., 2012, 64(3), 706-721.
[http://dx.doi.org/10.1124/pr.111.005637] [PMID: 22659329]
[17]
Zhang, L.; Wang, J.; Fu, Z.; Ai, Y.; Li, Y.; Wang, Y.; Wang, Y. Sevoflurane suppresses migration and invasion of glioma cells by regulating miR-146b-5p and MMP16. Artif. Cells Nanomed. Biotechnol., 2019, 47(1), 3306-3314.
[http://dx.doi.org/10.1080/21691401.2019.1648282] [PMID: 31385537]
[18]
Yu, B.; Gao, W.; Zhou, H.; Miao, X.; Chang, Y.; Wang, L.; Xu, M.; Ni, G. Propofol induces apoptosis of breast cancer cells by downregulation of miR-24 signal pathway. Dis. Markers, 2018, 21(3), 513-519.
[http://dx.doi.org/10.3233/CBM-170234] [PMID: 29103019]
[19]
Liu, W.Z.; Liu, N. Propofol inhibits lung cancer A549 cell growth and epithelial-mesenchymal transition process by upregulation of MicroRNA-1284. Oncol. Res., 2018, 27(1), 1-8.
[http://dx.doi.org/10.3727/096504018X15172738893959] [PMID: 29402342]
[20]
Zhang, W.; Wang, Y.; Zhu, Z.; Zheng, Y.; Song, B. Propofol inhibits proliferation, migration and invasion of gastric cancer cells by up-regulating microRNA-195. Int. J. Biol. Macromol., 2018, 120(Pt A), 975-984.
[http://dx.doi.org/10.1016/j.ijbiomac.2018.08.173]
[21]
Yi, W.; Li, D.; Guo, Y.; Zhang, Y.; Huang, B.; Li, X. Sevoflurane inhibits the migration and invasion of glioma cells by upregulating microRNA-637. Int. J. Mol. Med., 2016, 38(6), 1857-1863.
[http://dx.doi.org/10.3892/ijmm.2016.2797] [PMID: 27840895]
[22]
Jun, I.J.; Jo, J.Y.; Kim, J.I.; Chin, J.H.; Kim, W.J.; Kim, H.R.; Lee, E.H.; Choi, I.C. Impact of anesthetic agents on overall and recurrence-free survival in patients undergoing esophageal cancer surgery: A retrospective observational study. Sci. Rep., 2017, 7(1), 14020.
[http://dx.doi.org/10.1038/s41598-017-14147-9] [PMID: 29070852]
[23]
Yan, F.-C.; Wang, Q.-Q.; Ruan, Y.-H.; Ma, L.-J.; Jia, J.-T.; Jin, K.-W. Establishment and biological characteristics of lung cancer cell line XWLC-05. 2007, 26(1), 21-25.
[24]
Zhu, X.; Han, J.; Lan, H.; Lin, Q.; Wang, Y.; Sun, X. A novel circular RNA hsa_circRNA_103809/miR-377-3p/GOT1 pathway regulates cisplatin-resistance in Non-Small Cell Lung Cancer (NSCLC). BMC Cancer, 2020, 20(1), 1190.
[http://dx.doi.org/10.1186/s12885-020-07680-w] [PMID: 33276753]
[25]
Hu, B.; Zhang, H.; Wang, Z.; Zhang, F.; Wei, H.; Li, L. LncRNA CCAT1/miR-130a-3p axis increases cisplatin resistance in non-small-cell lung cancer cell line by targeting SOX4. Cancer Biol. Ther., 2017, 18(12), 974-983.
[http://dx.doi.org/10.1080/15384047.2017.1385679] [PMID: 29020498]
[26]
Kang, K.; Wang, Y. Sevoflurane inhibits proliferation and invasion of human ovarian cancer cells by regulating JNK and p38 MAPK signaling pathway. Drug Des. Devel. Ther., 2019, 13, 4451-4460.
[http://dx.doi.org/10.2147/DDDT.S223581] [PMID: 32021086]
[27]
Gao, C.; Shen, J.; Meng, Z.X.; He, X.F. Sevoflurane inhibits glioma cells proliferation and metastasis through miRNA-124-3p/ROCK1 axis. Pathol. Oncol. Res., 2020, 26(2), 947-954.
[http://dx.doi.org/10.1007/s12253-019-00597-1] [PMID: 30915607]
[28]
Yang, X.; Zheng, Y.T.; Rong, W. Sevoflurane induces apoptosis and inhibits the growth and motility of colon cancer in vitro and in vivo via inactivating Ras/Raf/MEK/ERK signaling. Life Sci., 2019, 239, 116916.
[http://dx.doi.org/10.1016/j.lfs.2019.116916] [PMID: 31626792]
[29]
Polivka, J., Jr; Janku, F. Molecular targets for cancer therapy in the PI3K/AKT/mTOR pathway. Pharmacol. Ther., 2014, 142(2), 164-175.
[http://dx.doi.org/10.1016/j.pharmthera.2013.12.004] [PMID: 24333502]
[30]
Nusse, R.; Clevers, H. Wnt/β-catenin signaling, disease, and emerging therapeutic modalities. Cell, 2017, 169(6), 985-999.
[http://dx.doi.org/10.1016/j.cell.2017.05.016] [PMID: 28575679]
[31]
Glen, J.B.I. The discovery and development of propofol anesthesia: The 2018 Lasker-DeBakey clinical medical research award. JAMA, 2018, 320(12), 1235-1236.
[http://dx.doi.org/10.1001/jama.2018.12756] [PMID: 30208399]
[32]
Walsh, C.T. Propofol: Milk of amnesia. Cell, 2018, 175(1), 10-13.
[http://dx.doi.org/10.1016/j.cell.2018.08.031] [PMID: 30217361]
[33]
Perry, N.J.S.; Buggy, D.; Ma, D. Can anesthesia influence cancer outcomes after surgery? JAMA Surg., 2019, 154(4), 279-280.
[http://dx.doi.org/10.1001/jamasurg.2018.4619] [PMID: 30649136]
[34]
Liu, Q.; Sheng, Z.; Cheng, C.; Zheng, H.; Lanuti, M.; Liu, R.; Wang, P.; Shen, Y.; Xie, Z. Anesthetic propofol promotes tumor metastasis in lungs via GABAA R-dependent TRIM21 modulation of Src expression. Adv. Sci. (Weinh.), 2021, 8(18), e2102079.
[http://dx.doi.org/10.1002/advs.202102079] [PMID: 34263559]
[35]
Mammoto, T.; Mukai, M.; Mammoto, A.; Yamanaka, Y.; Hayashi, Y.; Mashimo, T.; Kishi, Y.; Nakamura, H. Intravenous anesthetic, propofol inhibits invasion of cancer cells. Cancer Lett., 2002, 184(2), 165-170.
[http://dx.doi.org/10.1016/S0304-3835(02)00210-0] [PMID: 12127688]
[36]
Miao, Y.; Zhang, Y.; Wan, H.; Chen, L.; Wang, F. GABA-receptor agonist, propofol inhibits invasion of colon carcinoma cells. Biomed. Pharmacother., 2010, 64(9), 583-588.
[http://dx.doi.org/10.1016/j.biopha.2010.03.006] [PMID: 20888181]
[37]
Zhang, L.; Wang, N.; Zhou, S.; Ye, W.; Jing, G.; Zhang, M. Propofol induces proliferation and invasion of gallbladder cancer cells through activation of Nrf2. J. Exp. Clin. Cancer Res., 2012, 31(1), 66.
[http://dx.doi.org/10.1186/1756-9966-31-66] [PMID: 22901367]
[38]
Meng, C.; Song, L.; Wang, J.; Li, D.; Liu, Y.; Cui, X. Propofol induces proliferation partially via downregulation of p53 protein and promotes migration via activation of the Nrf2 pathway in human breast cancer cell line MDA-MB-231. Oncol. Rep., 2017, 37(2), 841-848.
[http://dx.doi.org/10.3892/or.2016.5332] [PMID: 28035403]
[39]
Ciechanowicz, S.; Zhao, H.; Chen, Q.; Cui, J.; Mi, E.; Mi, E.; Lian, Q.; Ma, D. Differential effects of sevoflurane on the metastatic potential and chemosensitivity of non-small-cell lung adenocarcinoma and renal cell carcinoma in vitro. Br. J. Anaesth., 2018, 120(2), 368-375.
[http://dx.doi.org/10.1016/j.bja.2017.11.066] [PMID: 29406185]
[40]
Fan, L.; Wu, Y.; Wang, J.; He, J.; Han, X. Sevoflurane inhibits the migration and invasion of colorectal cancer cells through regulating ERK/MMP-9 pathway by up-regulating miR-203. Eur. J. Pharmacol., 2019, 850, 43-52.
[http://dx.doi.org/10.1016/j.ejphar.2019.01.025] [PMID: 30685432]
[41]
Zhang, W.; Sheng, B.; Chen, S.; Zhao, H.; Wu, L.; Sun, Y.; Cui, J.; Zhu, X.; Ma, D. Sevoflurane enhances proliferation, metastatic potential of cervical cancer cells via the histone deacetylase 6 modulation in vitro. Anesthesiology, 2020, 132(6), 1469-1481.
[http://dx.doi.org/10.1097/ALN.0000000000003129] [PMID: 32412720]
[42]
Liang, H.; Yang, C.X.; Zhang, B.; Zhao, Z.L.; Zhong, J.Y.; Wen, X.J. Sevoflurane attenuates platelets activation of patients undergoing lung cancer surgery and suppresses platelets-induced invasion of lung cancer cells. J. Clin. Anesth., 2016, 35, 304-312.
[http://dx.doi.org/10.1016/j.jclinane.2016.08.008] [PMID: 27871548]
[43]
Zhang, Z.; Yu, W.; Zheng, M.; Liao, X.; Wang, J.; Yang, D.; Lu, W.; Wang, L.; Zhang, S.; Liu, H.; Zhou, X.Z.; Lu, K.P. Pin1 inhibition potently suppresses gastric cancer growth and blocks PI3K/AKT and Wnt/β-catenin oncogenic pathways. Mol. Carcinog., 2019, 58(8), 1450-1464.
[http://dx.doi.org/10.1002/mc.23027] [PMID: 31026381]
[44]
Zhang, L.N.; Zhao, L.; Yan, X.L.; Huang, Y.H. Loss of G3BP1 suppresses proliferation, migration, and invasion of esophageal cancer cells via Wnt/β-catenin and PI3K/AKT signaling pathways. J. Cell. Physiol., 2019, 234(11), 20469-20484.
[http://dx.doi.org/10.1002/jcp.28648] [PMID: 30989663]
[45]
Du, Q.; Zhang, X.; Zhang, X.; Wei, M.; Xu, H.; Wang, S. Propofol inhibits proliferation and epithelial-mesenchymal transition of MCF-7 cells by suppressing miR-21 expression. Artif. Cells Nanomed. Biotechnol., 2019, 47(1), 1265-1271.
[http://dx.doi.org/10.1080/21691401.2019.1594000] [PMID: 30942630]
[46]
Chen, M.; Zhou, L.; Liao, Z.; Ye, X.; Xuan, X.; Gu, B.; Lu, F. Sevoflurane inhibited osteosarcoma cell proliferation and invasion via targeting miR-203/WNT2B/Wnt/β-catenin axis. Cancer Manag. Res., 2019, 11, 9505-9515.
[http://dx.doi.org/10.2147/CMAR.S225911] [PMID: 31814757]
[47]
Gao, C.; He, X.F.; Xu, Q.R.; Xu, Y.J.; Shen, J. Sevoflurane downregulates insulin-like growth factor-1 to inhibit cell proliferation, invasion and trigger apoptosis in glioma through the PI3K/AKT signaling pathway. Anticancer Drugs, 2019, 30(7), e0744.
[PMID: 31305291]

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