Login Register Cart 0
Generic placeholder image

Recent Patents on Anti-Cancer Drug Discovery

Editor-in-Chief

ISSN (Print): 1574-8928
ISSN (Online): 2212-3970

Back
Journal Home About Journal Editorial Board Journal Insight Current Issue Volumes/Issues
Subscribe
Research Article

Lentiviral-Mediated Beclin-1 Overexpression Inhibits Cell Proliferation and Induces Autophagy of Human Esophageal Carcinoma Eca109 Cell Xenograft in Nude Mice

Author(s): Junhe Zhang* and Weihua Dong

Volume 15, Issue 1, 2020

Page: [70 - 77] Pages: 8

DOI: 10.2174/1574892814666191211130342

Price: $65

Abstract

Background: Esophageal carcinoma is one of the common malignant tumors in digestive tract. BECLIN-1 is a key gene that regulates autophagy, and its abnormal expression may be related with many human tumors. However, the mechanism of BECLIN-1 in esophageal carcinoma remains unknown.

Objective: In this study, we explored the effect of BECLIN-1 overexpression on tumor growth in mice with esophageal carcinoma and its mechanism.

Methods: Recombined lentiviral vector containing BECLIN-1 was used to transfect human esophageal carcinoma Eca109 cells and establish stable cell line. qRT-PCR was used to detect BECLIN-1 mRNA level in the transfected Eca109 cells, CCK-8 assay was used to detect cell proliferation. Beclin-1, P62 and LC3-II protein expression levels in Eca109 cells were detected using Western blot analysis. Subcutaneous xenograft nude mice model of human esophageal carcinoma was established, and the tumor growths in Beclin-1 group, control group and empty vector group were monitored. Beclin-1 protein expression in vivo was detected by immunohistochemistry.

Results: Beclin-1 mRNA and protein were overexpressed in Eca109 cells. Compared with empty vector group, the growth rate of cells transfected with BECLIN-1 decreased significantly. Compared with the control group and empty vector group, the expression level of P62 protein in beclin-1 group was significantly decreased, while the expression level of LC3-II protein was significantly increased. The tumor growth rate in nude mice of Beclin-1 group was significantly lower than that of the control group and empty vector group, and Beclin-1 protein was mainly expressed in Beclin-1 group in vivo.

Conclusion: BECLIN-1 can induce autophagy in esophageal carcinoma Eca109 cells, and it can significantly inhibit the growth of esophageal carcinoma.

Keywords: Autophagy, Beclin-1, esophageal carcinoma, lentiviral vector, proliferation, tumor growth.

« Previous Next »
[1]
Wang XC, Zhang TJ, Guo ZJ, et al. Overexpression of SKP2 inhibits the radiation-induced bystander effects of esophageal carcinoma. Int J Environ Res Public Health 2017; 14(2)E155
[http://dx.doi.org/10.3390/ijerph14020155] [PMID: 28178195]
[2]
Hayata K, Ojima T, Nakamori M, et al. Neoadjuvant chemotherapy with docetaxel, cisplatin and S-1 for resectable advanced esophageal cancer. Anticancer Res 2018; 38(9): 5267-73.
[http://dx.doi.org/10.21873/anticanres.12852] [PMID: 30194177]
[3]
Tustumi F, Kimura CM, Takeda FR, et al. Prognostic factors and survival analysis in esophageal carcinoma. Arq Bras Cir Dig 2016; 29(3): 138-41.
[http://dx.doi.org/10.1590/0102-6720201600030003] [PMID: 27759773]
[4]
Su X, Gao C, Shi F, et al. A microemulsion co-loaded with Schizandrin A-docetaxel enhances esophageal carcinoma treatment through overcoming multidrug resistance. Drug Deliv 2017; 24(1): 10-9.
[http://dx.doi.org/10.1080/10717544.2016.1225854] [PMID: 28155336]
[5]
Yu SB, Gao Q, Lin WW, Kang MQ. Proteomic analysis indicates the importance of TPM3 in esophageal squamous cell carcinoma invasion and metastasis. Mol Med Rep 2017; 15(3): 1236-42.
[http://dx.doi.org/10.3892/mmr.2017.6145] [PMID: 28138712]
[6]
Abu-Farsakh S, Wu T, Lalonde A, Sun J, Zhou Z. High expression of Claudin-2 in esophageal carcinoma and precancerous lesions is significantly associated with the bile salt receptors VDR and TGR5. BMC Gastroenterol 2017; 17(1): 33.
[http://dx.doi.org/10.1186/s12876-017-0590-0] [PMID: 28212604]
[7]
Nomura D, Zoncu R, Ward C, Fung S, Varma C, Fontaine B. Methods and compounds for targeted antophagy US201862647569. (2019).
[8]
Xue Y, Zhang Y, Ren J. A method and a device for predicting cellular autophagy phenotype CN109191467. (2019).
[9]
Manjithaya R, Mishra P, Santhi NS, Bats S, Ammanathan V, Chavalmane A. Method for modulating autophagy and applications thereof US2018369186. (2018).
[10]
Debnath J, Baehrecke EH, Kroemer G. Does autophagy contribute to cell death? Autophagy 2005; 1(2): 66-74.
[http://dx.doi.org/10.4161/auto.1.2.1738] [PMID: 16874022]
[11]
Mariño G, López-Otín C. Autophagy: molecular mechanisms, physiological functions and relevance in human pathology. Cell Mol Life Sci 2004; 61(12): 1439-54.
[http://dx.doi.org/10.1007/s00018-004-4012-4] [PMID: 15197469]
[12]
Chao X, Ni HM, Ding WX. Insufficient autophagy: a novel autophagic flux scenario uncovered by impaired liver TFEB-mediated lysosomal biogenesis from chronic alcohol-drinking mice. Autophagy 2018; 14(9): 1646-8.
[http://dx.doi.org/10.1080/15548627.2018.1489170] [PMID: 29969942]
[13]
Wang ZQ, Yang Y, Lu T, et al. Protective effect of autophagy inhibition on ischemia-reperfusion-induced injury of N2a cells. J Huazhong Univ Sci Technolog Med Sci 2013; 33(6): 810-6.
[http://dx.doi.org/10.1007/s11596-013-1203-y] [PMID: 24337840]
[14]
Wu BL, Wang D, Bai WJ, et al. An integrative framework to identify cell death-related microRNAs in esophageal squamous cell carcinoma. Oncotarget 2016; 7(35): 56758-66.
[http://dx.doi.org/10.18632/oncotarget.10779] [PMID: 27462775]
[15]
Hou W, Song L, Zhao Y, Liu Q, Zhang S. Inhibition of Beclin-1-mediated autophagy by microRNA-17-5p enhanced the radiosensitivity of glioma cells. Oncol Res 2017; 25(1): 43-53.
[http://dx.doi.org/10.3727/096504016X14719078133285] [PMID: 28081732]
[16]
Wang WY, Zhu H, Wu G, Zhou Y, Fan HK, Zhao GQ. Effect of autophagy-related gene Beclin 1 on growth of xenografts of human lung adenocarcinoma A549 cells in nude mice. Tumor 2011; 31(12): 1061-6.
[17]
Galluzzi L, Pietrocola F, Bravo-San Pedro JM, et al. Autophagy in malignant transformation and cancer progression. EMBO J 2015; 34(7): 856-80.
[http://dx.doi.org/10.15252/embj.201490784] [PMID: 25712477]
[18]
Zhao MJ, Tang H, Da L, et al. Sequence and application of promoter of human autophagic gene Beclin 1 CN102226182. (2011).
[19]
Jung CH, Ha TY, Ahn JY, Kim DH, Park JM. Method for screening for autophagy activator or inhibitor US2017226202. (2017).
[20]
Oh SJ, Kim YH, Kim SH, Park SS. Method for inhibiting tumor cells using cell-bound exopolysaccharide derived from lactobacillus species KR20110128596. (2011).
[21]
Oh SH, Choi YB, Kim JH, Weihl CC, Ju JS. Quantification of autophagy flux using LC3 ELISA. Anal Biochem 2017; 530: 57-67.
[http://dx.doi.org/10.1016/j.ab.2017.05.003] [PMID: 28477964]
[22]
Min Z, Ting Y, Mingtao G, et al. Monitoring autophagic flux using p62/SQSTM1 based luciferase reporters in glioma cells. Exp Cell Res 2018; 363(1): 84-94.
[http://dx.doi.org/10.1016/j.yexcr.2017.12.027] [PMID: 29289595]
[23]
Wang J, Garbutt C, Ma H, et al. Expression and role of autophagy-associated p62 (SQSTM1) in multidrug resistant ovarian cancer. Gynecol Oncol 2018; 150(1): 143-50.
[http://dx.doi.org/10.1016/j.ygyno.2018.04.557] [PMID: 29699801]
[24]
Masuda GO, Yashiro M, Kitayama K, et al. Clinicopathological correlations of autophagy-related proteins LC3, Beclin 1 and p62 in gastric cancer. Anticancer Res 2016; 36(1): 129-36.
[PMID: 26722036]
[25]
Depamphilis M, Sharma G, Marugan JJ, Ferrer M, Roy A. Autophagy modulators for use in treating cancer WO2019108665. (2019).
[26]
Gao W, Wang XJ, Liu XH, Zhao PY. Application of tripterine in inducing cancer cell autophagy and drug combination of tripterine and temozolomide CN109481448. (2019).
[27]
Goldsmith EJ, Piala AT, Potts MB. Compositions and methods for inhibition of autophagy US2017340636. (2017).
[28]
Hall TM, Tétreault MP, Hamilton KE, Whelan KA. Autophagy as a cytoprotective mechanism in esophageal squamous cell carcinoma. Curr Opin Pharmacol 2018; 41: 12-9.
[http://dx.doi.org/10.1016/j.coph.2018.04.003] [PMID: 29677645]
[29]
Sambrook J, Russell DW. Molecular cloning: A laboratory manual. 3rd ed. New York, NY: Cold Spring Harvor Laboratory Press 2001; pp. 27-35.
[30]
Zhang JH, Du AL, Wang L, Wang XY, Gao JH, Wang TY. Episomal lentiviral vector-mediated miR-145 overexpression inhibits proliferation and induces apoptosis of human esophageal carcinomas cells. Recent Patents Anticancer Drug Discov 2016; 11(4): 453-60.
[http://dx.doi.org/10.2174/1574892811666160822161157] [PMID: 27549139]
[31]
Zhang JH, Xia HB. Lentiviral-mediated overexpression of microRNA-141 promotes cell proliferation and inhibits apoptosis in human esophageal squamous cell carcinoma. Recent Patents Anticancer Drug Discov 2019; 14(2): 170-6.
[http://dx.doi.org/10.2174/1574892814666181231142136] [PMID: 30599110]
[32]
Fan JD, Jiang LX, Zhou ZW. Recombinant lentiviral vector preparation US2015056696. (2015).
[33]
Zhu HT, Ai DS, Tang HR, et al. Long-term results of paclitaxel plus cisplatin with concurrent radiotherapy for loco-regional esophageal squamous cell carcinoma. World J Gastroenterol 2017; 23(3): 540-6.
[http://dx.doi.org/10.3748/wjg.v23.i3.540] [PMID: 28210091]
[34]
Noguchi M, Yano T, Kato T, et al. Risk factors for intraoperative perforation during endoscopic submucosal dissection of superficial esophageal squamous cell carcinoma. World J Gastroenterol 2017; 23(3): 478-85.
[http://dx.doi.org/10.3748/wjg.v23.i3.478] [PMID: 28210084]
[35]
Saeki H, Tsutsumi S, Tajiri H, et al. Prognostic significance of postoperative complications after curative resection for patients with esophageal squamous cell carcinoma. Ann Surg 2017; 265(3): 527-33.
[http://dx.doi.org/10.1097/SLA.0000000000001692] [PMID: 28169928]
[36]
Chang P, Liu ZS, Yang CG. Application of molecular marker in diagnosis and treatment of esophageal squamous cell carcinoma CN105886629. (2016).
[37]
Yang CG, Song HT. Marker for diagnosis and treatment of esophageal squamous carcinoma CN106148533. (2016).
[38]
Langer R, Streutker CJ, Swanson PE. Autophagy and its current relevance to the diagnosis and clinical management of esophageal diseases. Ann N Y Acad Sci 2016; 1381(1): 113-21.
[http://dx.doi.org/10.1111/nyas.13190] [PMID: 27526024]
[39]
Lu C, Xie C. Radiation-induced autophagy promotes esophageal squamous cell carcinoma cell survival via the LKB1 pathway. Oncol Rep 2016; 35(6): 3559-65.
[http://dx.doi.org/10.3892/or.2016.4753] [PMID: 27109915]
[40]
Ouyang L, Shi Z, Zhao S, et al. Programmed cell death pathways in cancer: a review of apoptosis, autophagy and programmed necrosis. Cell Prolif 2012; 45(6): 487-98.
[http://dx.doi.org/10.1111/j.1365-2184.2012.00845.x] [PMID: 23030059]
[41]
Chen Y, Li X, Wu X, et al. Autophagy-related proteins LC3 and Beclin-1 impact the efficacy of chemoradiation on esophageal squamous cell carcinoma. Pathol Res Pract 2013; 209(9): 562-7.
[http://dx.doi.org/10.1016/j.prp.2013.06.006] [PMID: 23880165]
[42]
Wang WY, Fan HK, Li XY, Wu G, Zhao GQ, Li LW. Effects of autophagy-related gene Beclin-1 on autophagy and apoptosis of A549 lung cancer cells via esophageal cancer related gene 4 pathway. Chin J Exp Surg 2016; 33(3): 691-4.
[43]
Roesly HB, Khan MR, Chen HD, et al. The decreased expression of Beclin-1 correlates with progression to esophageal adenocarcinoma: the role of deoxycholic acid. Am J Physiol Gastrointest Liver Physiol 2012; 302(8): G864-72.
[http://dx.doi.org/10.1152/ajpgi.00340.2011] [PMID: 22301112]
[44]
Li SJ, Sun SJ, Gao J, Sun FB. Wogonin induces Beclin-1/PI3K and reactive oxygen species-mediated autophagy in human pancreatic cancer cells. Oncol Lett 2016; 12(6): 5059-67.
[http://dx.doi.org/10.3892/ol.2016.5367] [PMID: 28105213]
[45]
Park SH, Kang MK, Choi YJ, et al. α-Asarone blocks 7β-hydroxycholesterol-exposed macrophage injury through blocking elF2α phosphorylation and prompting beclin-1-dependent autophagy. Oncotarget 2017; 8(5): 7370-83.
[http://dx.doi.org/10.18632/oncotarget.14566] [PMID: 28088783]

Rights & Permissions Print Cite
Article Metrics
13
© 2024 Bentham Science Publishers | Privacy Policy