全部 标题 作者
关键词 摘要

OALib Journal期刊
ISSN: 2333-9721
费用：99美元
投递稿件

查看量下载量

相关文章

更多...

氯硝柳胺乙醇胺联合埃克替尼体外对肺腺癌HCC827细胞的协同抗肿瘤效应
In Vitro Synergistic Antitumor Effect of Niclosamide Ethanolamine Combined with Icotinib on HCC827 Cell

DOI: 10.12677/ACM.2020.107186, PP. 1211-1220

Keywords: 氯硝柳胺乙醇胺，盐酸埃克替尼，协同抗肿瘤
Chloronitramine Ethanolamine, Icotinib, Synergistic Antitumor

Full-Text   Cite this paper   Add to My Lib

Abstract:

目的：明确氯硝柳胺乙醇胺与盐酸埃克替尼联合应用在体外对人肺腺癌HCC827细胞的增殖抑制作用，探索两药合用是否具有协同抗肿瘤效应。方法：确定盐酸埃克替尼的半数抑制浓度、氯硝柳胺乙醇胺的半数抑制浓度，根据已确定的氯硝柳胺乙醇胺的IC50固定三个浓度，考察HCC827细胞增殖受到的抑制情况。绘制两药联合对HCC827细胞增殖的抑制曲线，检测两药是否有协同效应。结果：盐酸埃克替尼对HCC827细胞的IC50为0.61 μM。氯硝柳胺乙醇胺对HCC827细胞的IC50为0.46 μM。两药联用时，氯硝柳胺乙醇胺1.0 μM的处理组对细胞的抑制作用最明显，在极低浓度下细胞的生长即可被明显抑制。盐酸埃克替尼、氯硝柳胺均可以促进HCC827的细胞凋亡。联合应用组与单独应用组相比，HCC827细胞的晚期凋亡和坏死的比例都有所增加。结论：氯硝柳胺乙醇胺对人肺癌HCC827细胞株的增殖具有抑制作用，氯硝柳胺乙醇胺联合盐酸埃克替尼对人肺癌HCC827细胞有协同促进凋亡的作用。
Objective: To investigate the inhibitory effect of clonsalimine ethanolamine and ectinib hydrochloride on HCC827 cells in human lung adenocarcinoma in vitro and explore whether the combination of the two drugs has a synergistic anti-tumor effect. Methods: The half inhibitory concentration of ectinib hydrochloride and the half inhibitory concentration of niclosamine ethanolamine were determined, and the inhibition of HCC827 cell proliferation was investigated according to the fixed IC50 concentration of niclosamine ethanolamine. The inhibition curve of the combination of two drugs on HCC827 cell proliferation was drawn to detect the synergistic effect of the two drugs. Results: The IC50 of ectinib hydrochloride on HCC827 cells was 0.61 M. The IC50 of niclosamide ethanolamine against HCC827 cells was 0.46 M. When the two drugs were used together, the inhibition of cell growth was the most obvious in the treatment group of 1 M of niclosamide ethanolamine, and the growth of cells was significantly inhibited at very low concentration. Both ectinib hydrochloride and niclosamine could promote apoptosis of HCC827 cells. The ratio of late apoptosis and necrosis of HCC827 cells was increased in the combined group compared with the single group. Conclusion: Clonsalimine ethanolamine can inhibit the proliferation of HCC827 cell lines in human lung cancer, and clonsalimine ethanolamine combined with ectinib hydrochloride can promote the apoptosis of HCC827 cell lines in human lung cancer.

References

[1]  Zhang, X., Liu, S., Liu, Y., et al. (2017) Economic Burden for Lung Cancer Survivors in Urban China. International Journal of Environmental Research and Public Health, 14, 308.
https://doi.org/10.3390/ijerph14030308
[2]  Barnfield, P.C. and Ellis, P.M. (2016) Second-Line Treatment of Non-Small Cell Lung Cancer: New Developments for Tumours Not Harbouring Targetable Oncogenic Driver Mutations. Drugs, 76, 1321-1336.
https://doi.org/10.1007/s40265-016-0628-6
[3]  Ramalingam, S. and Belani, C. (2008) Systemic Chemotherapy for Advanced Non-Small Cell Lung Cancer: Recent Advances and Future Directions. Oncologist, 13, 5-13.
https://doi.org/10.1634/theoncologist.13-S1-5
[4]  Schiller, J.H., Harrington, D., Belani, C.P., et al. (2002) Comparison of Four Chemotherapy Regimens for Advanced Non-Small-Cell Lung Cancer. The New England Journal of Medicine, 346, 92-98.
https://doi.org/10.1056/NEJMoa011954
[5]  Greenhalgh, J., Dwan, K., Boland, A., et al. (2016) First-Line Treatment of Advanced Epidermal Growth Factor Receptor (EGFR) Mutation Positive Non-Squamous Non-Small Cell Lung Cancer. Cochrane Database of Systematic Reviews, 5, CD010383.
https://doi.org/10.1002/14651858.CD010383.pub2
[6]  Shi, Y., Zhang, L., Liu, X., et al. (2013) Icotinib versus Gefitinib in Previously Treated Advanced Non-Small-Cell Lung Cancer (ICOGEN): A Randomised, Double-Blind Phase 3 Non-Inferiority Trial. Lancet Oncology, 14, 953-961.
https://doi.org/10.1016/S1470-2045(13)70355-3
[7]  Li, L., Han, R., Xiao, H., et al. (2014) Metformin Sensitizes EGFR-TKI-Resistant Human Lung Cancer Cells in Vitro and in Vivo through Inhibition of IL-6 Signaling and EMT Reversal. Clinical Cancer Research, 20, 2714-2726.
https://doi.org/10.1158/1078-0432.CCR-13-2613
[8]  Li, J. and Wang, X.H. (2020) Combined Treatment with N-Acetylcysteine and Gefitinib Overcomes Drug Resistance to Gefitinib in NSCLC Cell Line. Cancer Medicine, 9, 1495-1502.
https://doi.org/10.1002/cam4.2610
[9]  Zhang, Y., Lv, C., Dong, Y., et al. (2020) Aspirin-Targeted PD-L1 in Lung Cancer Growth Inhibition. Thoracic Cancer, 11, 1587-1593.
[10]  Chuang, S.-E. (2013) Aspirin Antagonizes the Cytotoxic Effect of Methotrexate in Lung Cancer Cells. Oncology Reports, 30, 1497-1505.
https://doi.org/10.3892/or.2013.2561
[11]  Andrews, P., Thyssen, J. and Lorke, D. (1982) The Biology and Toxicology of Molluscicides, Bayluscide. Pharmacology & Therapeutics, 19, 245-295.
https://doi.org/10.1016/0163-7258(82)90064-X
[12]  Al-Hadiya, B.M.H. (2005) Niclosamide: Comprehensive Profile. Profiles of Drug Substances, Excipients and Related Methodology, 32, 67-96.
https://doi.org/10.1016/S0099-5428(05)32002-8
[13]  Jin, Y., Lu, Z., Ding, K., et al. (2010) Antineoplastic Mechanisms of Niclosamide in Acute Myelogenous Leukemia Stem Cells: Inactivation of the NF-kB Pathway and Generation of Reactive Oxygen Species. Cancer Research, 70, 2516-2527.
https://doi.org/10.1158/0008-5472.CAN-09-3950
[14]  Osada, T., Chen, M., Yang, X.Y., et al. (2011) Antihelminth Compound Niclosamide Downreguates WNT Signaling and Elicits Antitumor Responses in Tumors with Activating APC Mutations. Cancer Research, 71, 4172-4182.
https://doi.org/10.1158/0008-5472.CAN-10-3978
[15]  Sack, U., Walther, W., Scudiero, D., et al. (2011) Novel Effect of Antihelminthic Niclosamide on S100A4-Mediated Metastatic Progression in Colon Cancer. Journal of the National Cancer Institute, 103, 1018-1036.
https://doi.org/10.1093/jnci/djr190
[16]  Ren, X., Duan, L., He, Q., et al. (2010) Identification of Niclosamide as a New Small-Molecule Inhibitor of the STAT3 Signaling Pathway. ACS Medicinal Chemistry Letters, 1, 454-459.
https://doi.org/10.1021/ml100146z
[17]  Liu, Z., Li, Y., Lv, C., et al. (2016) Anthelmintic Drug Niclosamide Enhances the Sensitivity of Chronic Myeloid Leukemia Cells to Dasatinib through Inhibiting Erk/Mnk1/eIF4E Pathway. Biochemical and Biophysical Research Communications, 478, 893-899.
https://doi.org/10.1016/j.bbrc.2016.08.047
[18]  Arend, R.C., Londo？o-Joshi, A.I., Samant, R.S., et al. (2014) Inhibition of Wnt/β-Catenin Pathway by Niclosamide: A Therapeutic Target for Ovarian Cancer. Gynecologic Oncology, 134, 112-120.
https://doi.org/10.1016/j.ygyno.2014.04.005
[19]  Park, S.J., Shin, J.H., Kang, H., et al. (2011) Niclosamide Induces Mitochondria Fragmentation and Promotes Both Apoptotic and Autophagic Cell Death. BMB Reports, 44, 517-522.
https://doi.org/10.5483/BMBRep.2011.44.8.517
[20]  Li, R., Hu, Z., Sun, S.Y., et al. (2013) Niclosamide Overcomes Acquired Resistance to Erlotinib through Suppression of STAT3 in Non-Small Cell Lung Cancer. Molecular Cancer Therapeutics, 12, 2200-2212.
https://doi.org/10.1158/1535-7163.MCT-13-0095
[21]  Li, R., You, S., Hu, Z., et al. (2013) Inhibition of STAT3 by Niclosamide Synergizes with Erlotinib against Head and Neck Cancer. PLoS One, 8, e74670.
https://doi.org/10.1371/journal.pone.0074670
[22]  Li, Y., Li, P.K., Roberts, M.J., et al. (2014) Multi-Targeted Therapy of Cancer by Niclosamide: A New Application for an Old Drug. Cancer Letters, 349, 8-14.
https://doi.org/10.1016/j.canlet.2014.04.003
[23]  Yo, Y.-T., Lin, Y.-W., Wang, Y.-C., et al. (2012) Growth Inhibition of Ovarian Tumor-Initiating Cells by Niclosamide. Molecular Cancer Therapeutics, 11, 1703-1712.
https://doi.org/10.1158/1535-7163.MCT-12-0002
[24]  Liu, J., Chen, X., Ward, T., et al. (2016) Combined Niclosamide with Cisplatin Inhibits Epithelial Mesenchymal Transition and Tumor Growth in Cisplatin-Resistant Triple-Negative Breast Cancer. Tumor Biology, 37, 9825-9835.
https://doi.org/10.1007/s13277-015-4650-1
[25]  Wang, Y.-C., Chao, T.-K., Chang, C.-C., et al. (2013) Drug Screening Identifies Niclosamide as an Inhibitor of Breast Cancer Stem-Like Cells. PLoS One, 8, e74538.
https://doi.org/10.1371/journal.pone.0074538
[26]  Chen, B., Wei, W., Ma, L., et al. (2017) Computational Discovery of Niclosamide Ethanolamine, a Repurposed Drug Candidate That Reduces Growth of Hepatocellular Carcinoma Cells in Vitro and in Mice by Inhibiting Cell Division Cycle 37 Signaling. Gastroenterology, 152, 2022-2036.
https://doi.org/10.1053/j.gastro.2017.02.039
[27]  Lee, M.-C., Chen, Y.-K., Hsu, Y.-J., et al. (2020) Niclosamide Inhibits the Cell Proliferation and Enhances the Responsiveness of Esophageal Cancer Cells to Chemotherapeutic Agents. Oncology Reports, 43, 549-561.
[28]  Chang, X., Zhen, X., Liu, J., et al. (2017) The Antihelmenthic Phosphate Niclosamide Impedes Renal Fibrosis by Inhibiting Homeodomain-Interacting Protein Kinase 2 Expression. Kidney International, 92, 612-624.
https://doi.org/10.1016/j.kint.2017.01.018
[29]  Kim, M.-O., Choe, M.H., Yoon, Y.N., et al. (2017) Antihelminthic Drug Niclosamide Inhibits CIP2A and Reactivates Tumor Suppressor Protein Phosphatase 2A in Non-Small Cell Lung Cancer Cells. Biochemical Pharmacology, 144, 78-89.
https://doi.org/10.1016/j.bcp.2017.08.009
[30]  Gahr, S., Stoehr, R., Geissinger, E., et al. (2013) EGFR Mutational Status in a Large Series of Caucasian European NSCLC Patients: Data from Daily Practice. British Journal of Cancer, 109, 1821-1828.
https://doi.org/10.1038/bjc.2013.511
[31]  Lee, M.C., Chen, Y.K., Hsu, Y.J., et al. (2020) Niclosamide Inhibits the CELL proliferation and Enhances the Responsiveness of Esophageal Cancer Cells to Chemotherapeutic Agents. Oncology Reports, 43, 549-561.
https://doi.org/10.3892/or.2019.7449
[32]  Pan, J.-X., Ding, K. and Wang, C.-Y. (2012) Niclosamide, an Old Antihelminthic Agent, Demonstrates Antitumor Activity by Blocking Multiple Signaling Pathways of Cancer Stem Cells. Chinese Journal of Cancer, 31, 178-184.
https://doi.org/10.5732/cjc.011.10290
[33]  Chen, W., Mook Jr., R.A., Premont, R.T. and Wang, J.B. (2018) Niclosamide: Beyond an Antihelminthic Drug. Cellular Signalling, 41, 89-96.
https://doi.org/10.1016/j.cellsig.2017.04.001
[34]  You, S., Li, R., Park, D., et al. (2014) Disruption of STAT3 by Niclosamide Reverses Radioresistance of Human Lung Cancer. Molecular Cancer Therapeutics, 13, 606-616.
https://doi.org/10.1158/1535-7163.MCT-13-0608
[35]  Chai, W.-H., Li, Y.-R., Lin, S.-H., et al. (2020) In Vitro Antihelminthic Niclosamide Induces Autophagy and Delayed Apoptosis in Human Non-small Lung Cancer Cells and. Anticancer Research, 40, 1405-1417.
https://doi.org/10.21873/anticanres.14082
[36]  左瑜芳, 杨东雁, 徐祖敏, 等. 氯硝柳胺对肺癌细胞株顺铂敏感性的影响[J]. 广东医科大学学报, 2017, 35(2): 144-147.
[37]  Zuo, Y., Yang, D., Yu, Y., et al. (2018) Niclosamide Enhances the Cytotoxic Effect of Cisplatin in Cisplatin-Resistant Human Lung Cancer Cells via Suppression of Lung Resistance-Related Protein and c-myc. Molecular Medicine Reports, 17, 3497-3502.
[38]  Helfman, D.M., Kim, E.J., Lukanidin, E. and Grigorian, M. (2005) The Metastasis Associated Protein S100A4: Role in Tumour Progression and Metastasis. British Journal of Cancer, 92, 1955-1958.
https://doi.org/10.1038/sj.bjc.6602613

Full-Text

Contact Us

service@oalib.com

QQ:3279437679

WhatsApp +8615387084133