Influence of delta-like 1 on chemotherapeutic sensitivity of small cell lung cancer

Authors

  • Huanxin Liu Department of Pathology, Guangdong Provincial Corps Hospital of Chinese People's Armed Police Forces, Guangzhou Medical College, Guangzhou, 268 Yanling Road, Guangzhou 510507
  • Yan Zhang Department of Pathology, Guangdong Provincial Corps Hospital of Chinese People's Armed Police Forces, Guangzhou Medical College, Guangzhou, 268 Yanling Road, Guangzhou 510507
  • Zuoping Huang Department of Oncology, Guangdong Provincial Corps Hospital of Chinese People's Armed Police Forces, Guangzhou Medical College, Guangzhou, 268 Yanling Road, Guangzhou 510507
  • Linlang Guo Department of Pathology, Zhujiang Hospital, Southern Medical University, 253 Gongye Road, Guangzhou 510282

DOI:

https://doi.org/10.3329/bjp.v8i2.14234

Keywords:

Delta-like 1, Multidrug resistance, Small cell lung cancer

Abstract

Our study investigated the role of delta-like 1 (DLL1) in multi-drug resistance of small cell lung cancer. Differentially expressed genes were detected in resistant small cell lung cancer H69AR cells and sensitive small cell lung cancer H69 cells by microarray. DLL1 expression in H69 cells and H69AR cells was further confirmed by RT-PCR and Western blot assay. eGFP-RNA was employed to up-regulate DDL1 expressing in H69AR cells (H69AR-eGFP-DLL1) by transfection. These cells were treated with different chemotherapeutics (ADM, DDP, and VP-16). Cell viability was detected. Cell cycle and apoptosis rate were determined. The DLL1 expression was significantly decreased in H69AR cells when compared with H69 cells. Over-expression of DLL1 increased the sensitivity of H69AR cells to chemotherapy, which was characterized by increase in apoptosis and arrest in G0/G1 phase. Our results demonstrate that up-regulation of DLL1 expression in small cell lung cancer cells may increase their sensitivity to chemotherapeutic agents.

Downloads

Download data is not yet available.
Abstract
148
Download
96 Read
1

References

Bachmann E, Krogh TN, Hojrup P, Skjodt K, Teisner B. Mouse fetal antigen 1 (mfa1), the circulating gene product of mdlk, pref-1 and scp-1: Isolation, characterization and biology. J Reprod Fertil. 1996; 107: 279-85.

Begum A, Kim Y, Lin Q, Yun Z. Dlk1, delta-like 1 homolog (drosophila), regulates tumor cell differentiation in vivo. Cancer Lett. 2012; 318: 26-33.

Berezikov E, Guryev V, van de Belt J, Wienholds E, Plasterk RH, Cuppen E. Phylogenetic shadowing and computational identification of human microrna genes. Cell 2005; 120: 21-24.

Bommer GT, Gerin I, Feng Y, Kaczorowski AJ, Kuick R, Love RE, Zhai Y, Giordano TJ, Qin ZS, Moore BB, MacDougald OA, Cho KR, Fearon ER. P53-mediated activation of mirna34 candidate tumor-suppressor genes. Curr Biol. 2007; 17: 1298-307.

Bordonaro M, Tewari S, Atamna W, Lazarova DL. The notch ligand delta-like 1 integrates inputs from tgfbeta/activin and wnt pathways. Exp Cell Res. 2011; 317: 1368-81.

Bridges E, Oon CE, Harris A. Notch regulation of tumor angiogenesis. Future Oncol. 2011; 7: 569-88.

Chang TC, Wentzel EA, Kent OA, Ramachandran K, Mullendore M, Lee KH, Feldmann G, Yamakuchi M, Ferlito M, Lowenstein CJ, Arking DE, Beer MA, Maitra A, Mendell JT. Transactivation of mir-34a by p53 broadly influences gene expression and promotes apoptosis. Mol Cell. 2007; 26: 745-52.

Chen F, Hu SJ. Effect of microrna-34a in cell cycle, differentiation, and apoptosis: A review. J Biochem Mol Toxicol. 2012; 26: 79-86.

Chen YR, Feng F, Yin DD, Liang YM, Han H. [role of delta-like 1 in differentiation and antigen presentation of mouse bone marrow-derived dendritic cells]. Zhongguo Shi Yan Xue Ye Xue Za Zhi. 2010; 18: 704-08.

Chute JP, Chen T, Feigal E, Simon R, Johnson BE. Twenty years of phase iii trials for patients with extensive-stage small-cell lung cancer: Perceptible progress. J Clin Oncol. 1999; 17: 1794-801.

de Antonellis P, Medaglia C, Cusanelli E, Andolfo I, Liguori L, De Vita G, Carotenuto M, Bello A, Formiggini F, Galeone A, De Rosa G, Virgilio A, Scognamiglio I, Sciro M, Basso G, Schulte JH, Cinalli G, Iolascon A, Zollo M. Mir-34a targeting of notch ligand delta-like 1 impairs cd15+/cd133+ tumor-propagating cells and supports neural differentiation in medulloblastoma. PLoS One. 2011; 6: e24584.

Denli AM, Tops BB, Plasterk RH, Ketting RF, Hannon GJ. Processing of primary micrornas by the microprocessor complex. Nature 2004; 432: 231-35.

Estrach S, Cordes R, Hozumi K, Gossler A, Watt FM. Role of the notch ligand delta1 in embryonic and adult mouse epidermis. J Invest Dermatol. 2008; 128: 825-32.

Falix FA, Aronson DC, Lamers WH, Hiralall JK, Seppen J. Dlk1, a serum marker for hepatoblastoma in young infants. Pediatr Blood Cancer. 2012; 59: 743-45.

Flahaut M, Meier R, Coulon A, Nardou KA, Niggli FK, Martinet D, Beckmann JS, Joseph JM, Muhlethaler-Mottet A, Gross N. The wnt receptor fzd1 mediates chemoresistance in neuroblastoma through activation of the wnt/beta-catenin pathway. Oncogene 2009; 28: 2245-56.

Groth C, Fortini ME. Therapeutic approaches to modulating notch signaling: Current challenges and future prospects. Semin Cell Dev Biol. 2012; 23: 465-72.

Han J, Hendzel MJ, Allalunis-Turner J. Notch signaling as a therapeutic target for breast cancer treatment? Breast Cancer Res. 2011; 13: 210.

He L, He X, Lim LP, de Stanchina E, Xuan Z, Liang Y, Xue W, Zender L, Magnus J, Ridzon D, Jackson AL, Linsley PS, Chen C, Lowe SW, Cleary MA, Hannon GJ. A microrna component of the p53 tumour suppressor network. Nature 2007; 447: 1130-34.

Huang Y, Lin L, Shanker A, Malhotra A, Yang L, Dikov MM, Carbone DP. Resuscitating cancer immunosurveillance: Selective stimulation of dll1-notch signaling in t cells rescues t-cell function and inhibits tumor growth. Cancer Res. 2011; 71: 6122-31.

Jubb AM, Browning L, Campo L, Turley H, Steers G, Thurston G, Harris AL, Ansorge O. Expression of vascular notch ligands delta-like 4 and jagged-1 in glioblastoma. Histopathology 2012; 60: 740-47.

Kim Y. The effects of nutrient depleted microenvironments and delta-like 1 homologue (dlk1) on apoptosis in neuroblastoma. Nutr Res Pract. 2010; 4: 455-61.

Kolev V, Kacer D, Trifonova R, Small D, Duarte M, Soldi R, Graziani I, Sideleva O, Larman B, Maciag T, Prudovsky I. The intracellular domain of notch ligand delta1 induces cell growth arrest. FEBS Lett. 2005; 579: 5798-802.

Lodygin D, Tarasov V, Epanchintsev A, Berking C, Knyazeva T, Korner H, Knyazev P, Diebold J, Hermeking H. Inactivation of mir-34a by aberrant cpg methylation in multiple types of cancer. Cell Cycle. 2008; 7: 2591-600.

Oon CE, Harris AL. New pathways and mechanisms regulating and responding to delta-like ligand 4-notch signalling in tumour angiogenesis. Biochem Soc Trans. 2011; 39: 1612-18.

Pang RT, Leung CO, Lee CL, Lam KK, Ye TM, Chiu PC, Yeung WS. Microrna-34a is a tumor suppressor in choriocarcinoma via regulation of delta-like1. BMC Cancer. 2013; 13: 25.

Pang RT, Leung CO, Ye TM, Liu W, Chiu PC, Lam KK, Lee KF, Yeung WS. Microrna-34a suppresses invasion through downregulation of notch1 and jagged1 in cervical carcinoma and choriocarcinoma cells. Carcinogenesis 2010; 31: 1037-44.

Piazzi G, Fini L, Selgrad M, Garcia M, Daoud Y, Wex T, Malfertheiner P, Gasbarrini A, Romano M, Meyer RL, Genta RM, Fox JG, Boland CR, Bazzoli F, Ricciardiello L. Epigenetic regulation of delta-like1 controls notch1 activation in gastric cancer. Oncotarget. 2011; 2: 1291-301.

Sandler AB. Chemotherapy for small cell lung cancer. Semin Oncol. 2003; 30: 9-25.

Smas CM, Sul HS. Pref-1, a protein containing EGF-like repeats, inhibits adipocyte differentiation. Cell 1993; 73: 725-34.

Wang Y, Kim KA, Kim JH, Sul HS. Pref-1, a preadipocyte secreted factor that inhibits adipogenesis. J Nutr. 2006; 136: 2953-56.

Xu X, Liu RF, Zhang X, Huang LY, Chen F, Fei QL, Han ZG. Dlk1 as a potential target against cancer stem/progenitor cells of hepatocellular carcinoma. Mol Cancer Ther. 2012; 11: 629-38.

Yin D, Xie D, Sakajiri S, Miller CW, Zhu H, Popoviciu ML, Said JW, Black KL, Koeffler HP. Dlk1: Increased expression in gliomas and associated with oncogenic activities. Oncogene 2006; 25: 1852-61.

Zhang JP, Qin HY, Wang L, Liang L, Zhao XC, Cai WX, Wei YN, Wang CM, Han H. Overexpression of notch ligand dll1 in b16 melanoma cells leads to reduced tumor growth due to attenuated vascularization. Cancer Lett. 2011; 309: 220-27.

Downloads

Additional Files

Published

2013-04-22

How to Cite

Liu, H., Y. Zhang, Z. Huang, and L. Guo. “Influence of Delta-Like 1 on Chemotherapeutic Sensitivity of Small Cell Lung Cancer”. Bangladesh Journal of Pharmacology, vol. 8, no. 2, Apr. 2013, pp. 171-6, doi:10.3329/bjp.v8i2.14234.

Issue

Vol. 8 No. 2 (2013)

Section

Research Articles

License

Authors who publish with this journal agree to the following terms:

  1. Authors retain copyright and grant the journal right of first publication with the work simultaneously licensed under a Creative Commons Attribution License that allows others to share the work with an acknowledgement of the work's authorship and initial publication in this journal.
  2. Authors are able to enter into separate, additional contractual arrangements for the non-exclusive distribution of the journal's published version of the work (e.g., post it to an institutional repository or publish it in a book), with an acknowledgement of its initial publication in this journal.
  3. Authors are permitted and encouraged to post their work online (e.g., in institutional repositories or on their website) prior to and during the submission process, as it can lead to productive exchanges, as well as earlier and greater citation of published work (See The Effect of Open Access).