Generic placeholder image

Current Pharmaceutical Design

Editor-in-Chief

ISSN (Print): 1381-6128
ISSN (Online): 1873-4286

Research Article

Effect of Raltitrexed on ECA109 Cellular Radiosensitivity and its Mechanism in Esophageal Cancer

Author(s): Li-Ben Xu, Chao-Yang Wu, Yan Wang and Ju-Ying Zhou*

Volume 30, Issue 19, 2024

Published on: 23 April, 2024

Page: [1519 - 1529] Pages: 11

DOI: 10.2174/0113816128286282240405064210

Price: $65

Open Access Journals Promotions 2
Abstract

Background: To investigate the effect of raltitrexed + X-ray irradiation on esophageal cancer ECA109 cells and analyze the potential action mechanism.

Methods: The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay was used to analyze the inhibitory effect of raltitrexed on cell proliferation. The effect of raltitrexed on radiosensitivity was studied through a clone-forming experiment. The scratch assay and invasion test were performed to understand the cell migration and invasion abilities. The apoptosis rate change was measured using a flow cytometer, and Western Blotting was used to determine the expression of B cell lymphoma-2 (Bcl-2) and Bcl2-associated X protein (Bax) in each group.

Results: Raltitrexed significantly inhibited ECA109 proliferation in a time-dose-dependent manner; there were significant differences among different concentrations and times of action. The results of the clone-forming experiment showed a sensitization enhancement ratio of 1.65, and this demonstrated a radiosensitization effect. After the combination of raltitrexed with X-ray, the cell migration distance was shortened, and the number of cells penetrating the membrane was reduced.

Conclusion: Raltitrexed can inhibit the growth of esophageal cancer ECA109 cells and has a radiosensitization effect.

Keywords: Raltitrexed, radiosensitization, esophageal cancer, migration and invasion, apoptosis, Bax/Bcl-2 pathway.

[1]
Yano T. Paradox of age-specific incidence rates of second primary cancer in individuals with esophageal cancer. J Gastroenterol 2020; 55(6): 664-5.
[http://dx.doi.org/10.1007/s00535-020-01687-7] [PMID: 32285194]
[2]
Gong J, Wang MM, Zhang XH, et al. Efficacy and safety of huachansu capsules for the treatment of esophageal cancer: A systematic review and meta-analysis. World J Tradit Chin Med 2023; 9(3): 270-7.
[http://dx.doi.org/10.4103/2311-8571.355009]
[3]
Kelly RJ. Emerging multimodality approaches to treat localized esophageal cancer. J Natl Compr Canc Netw 2019; 17(8): 1009-14.
[http://dx.doi.org/10.6004/jnccn.2019.7337] [PMID: 31390584]
[4]
Chen JQ, Lin Y, Su TF, et al. Clinical study of non-operative staging of esophageal squamous cell carcinoma underwent intensity- modulated radiotherapy combined with chemotherapy. Chin J Radiat Oncol 2017; 26: 155-9.
[5]
Tang JC, Zhao J, Long F, et al. Efficacy of shikonin against esophageal cancer cells and its possible mechanisms in vitro and in vivo. J Cancer 2018; 9(1): 32-40.
[http://dx.doi.org/10.7150/jca.21224] [PMID: 29290767]
[6]
Long L, Pang XX, Lei F, et al. SLC52A3 expression is activated by NF-κB p65/Rel-B and serves as a prognostic biomarker in esophageal cancer. Cell Mol Life Sci 2018; 75(14): 2643-61.
[http://dx.doi.org/10.1007/s00018-018-2757-4] [PMID: 29428966]
[7]
Sun HH, He LM, Zhang JD, Shi DM. Effects of raltitrexed combined with nedaplatin on the expression of proline rich 11 and squamous cell carcinoma antigen in patients with esophageal squamous cell carcinoma. Oncol Prog 2020; 18: 1345-8.
[8]
Wang S, Li X, Qian TK. Synergistic effect of Raltetrexed combined with X-ray irradiation on human laryngeal carcinoma cells Hep-2. J Clin Med 2017; 24: 879-83.
[9]
Stausbøl-Grøn B, Nielsen OS, Bentzen SM, Overgaard J. Selective assessment of in vitro radiosensitivity of tumour cells and fibroblasts from single tumour biopsies using immunocytochemical identification of colonies in the soft agar clonogenic assay. Radiother Oncol 1995; 37(2): 87-99.
[http://dx.doi.org/10.1016/0167-8140(95)98589-D] [PMID: 8747932]
[10]
Franken NAP, Rodermond HM, Stap J, Haveman J, van Bree C. Clonogenic assay of cells in vitro. Nat Protoc 2006; 1(5): 2315-9.
[http://dx.doi.org/10.1038/nprot.2006.339] [PMID: 17406473]
[11]
Willers H, Dahm-Daphi J, Powell SN. Repair of radiation damage to DNA. Br J Cancer 2004; 90(7): 1297-301.
[http://dx.doi.org/10.1038/sj.bjc.6601729] [PMID: 15054444]
[12]
Wu G, Chen G, Zhou J, Zhu H, Chu J, Zhang F. Liriodenine enhances radiosensitivity in esophageal cancer ECA-109 cells by inducing apoptosis and G2/M arrest. Oncol Lett 2018; 16(4): 5020-6.
[http://dx.doi.org/10.3892/ol.2018.9253] [PMID: 30250568]
[13]
Desvoyes B, Gutierrez C. Roles of plant retinoblastoma protein: Cell cycle and beyond. EMBO J 2020; 39(19): e105802.
[http://dx.doi.org/10.15252/embj.2020105802] [PMID: 32865261]
[14]
Li J, Yang CX, Mei ZJ, et al. Involvement of cdc25c in cell cycle alteration of a radioresistant lung cancer cell line established with fractionated ionizing radiation. Asian Pac J Cancer Prev 2013; 14(10): 5725-30.
[http://dx.doi.org/10.7314/APJCP.2013.14.10.5725] [PMID: 24289569]
[15]
Wu X, Roth JA, Zhao H, et al. Cell cycle checkpoints, DNA damage/repair, and lung cancer risk. Cancer Res 2005; 65(1): 349-57.
[http://dx.doi.org/10.1158/0008-5472.349.65.1] [PMID: 15665313]
[16]
Solier S, Zhang YW, Ballestrero A, Pommier Y, Zoppoli G. DNA damage response pathways and cell cycle checkpoints in colorectal cancer: Current concepts and future perspectives for targeted treatment. Curr Cancer Drug Targets 2012; 12(4): 356-71.
[http://dx.doi.org/10.2174/156800912800190901] [PMID: 22385513]
[17]
Chen Z, Wu Y, Meng Q, Xia Z. Elevated microRNA-25 inhibits cell apoptosis in lung cancer by targeting RGS3. In Vitro Cell Dev Biol Anim 2016; 52(1): 62-7.
[http://dx.doi.org/10.1007/s11626-015-9947-2] [PMID: 26416661]
[18]
Bunn PA Jr, Gaspar LE, Weyant MJ, Mitchell JD. Neoadjuvant combination chemotherapy for unresectable stage III non–small cell lung cancer. Cancer 2016; 122(5): 674-5.
[http://dx.doi.org/10.1002/cncr.29797] [PMID: 26700372]
[19]
Hogg SJ, Newbold A, Vervoort SJ, et al. BET inhibition induces apoptosis in aggressive b-cell lymphoma via epigenetic regulation of BCL-2 family members. Mol Cancer Ther 2016; 15(9): 2030-41.
[http://dx.doi.org/10.1158/1535-7163.MCT-15-0924] [PMID: 27406984]
[20]
Hahnvajanawong C, Wattanawongdon W, Chomvarin C, et al. Synergistic effects of isomorellin and forbesione with doxorubicin on apoptosis induction in human cholangiocarcinoma cell lines. Cancer Cell Int 2014; 14(1): 68.
[http://dx.doi.org/10.1186/1475-2867-14-68] [PMID: 25866479]
[21]
Karimi F, Karimi-Maleh H, Rouhi J, et al. Revolutionizing cancer monitoring with carbon-based electrochemical biosensors. Environ Res 2023; 239(Pt 2): 117368.
[http://dx.doi.org/10.1016/j.envres.2023.117368] [PMID: 37827366]
[22]
Tao C, Rouhi J. A biosensor based on graphene oxide nanocomposite for determination of carcinoembryonic antigen in colorectal cancer biomarker. Environ Res 2023; 238(Pt 1): 117113.
[http://dx.doi.org/10.1016/j.envres.2023.117113] [PMID: 37696325]

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