Skip to main content
Erschienen in: Cancer Chemotherapy and Pharmacology 5/2018

14.03.2018 | Original Article

Cisplatin suppresses proliferation, migration and invasion of nasopharyngeal carcinoma cells in vitro by repressing the Wnt/β-catenin/Endothelin-1 axis via activating B cell translocation gene 1

verfasst von: Peng Yin, Guizhen Song, Zhenhua Jiang

Erschienen in: Cancer Chemotherapy and Pharmacology | Ausgabe 5/2018

Einloggen, um Zugang zu erhalten

Abstract

Purpose

Nasopharyngeal carcinoma (NPC) is one of the most commonly diagnosed cancers worldwide with significantly high prevalence in Southern China. Chemoprevention of cancer with alkylating agent compounds could potentially reverse, suppress, or prevent cancer progression. Cisplatin (CIS) is an antineoplastic or cytotoxic platinum-based drug used for chemotherapy of different types of human cancers such as NPC. Nevertheless, the effects of CIS on the migration and invasion of human NPC cells and the underlying molecular mechanisms have not yet been fully scrutinized.

Methods

In this work, we tested the effect of CIS on the proliferation, migration and invasion of NPC cells. The results exhibited that this drug exerts remarkable inhibitory effects on the proliferation, migration and invasion of NPC cells in a dose-dependent manner. Western blotting and real time RT-PCR were used for expression analyses.

Results

We found that CIS treatment led to a dose-dependent inhibition of Endothelin-1 (ET1) expression, at protein as well as mRNA levels in NPC cells. CIS was also found to activate the expression of BTG1 in NPC cells. Moreover, mechanistic analyses revealed that CIS increased the expression of B cell translocation gene 1 (BTG1) to suppress the expression of ET1. Furthermore, we show that ET1 could not be induced in CIS-resistant cells with suppressed BTG1 expression, and subsequently demote the proliferation, migration and invasion of NPC cells.

Conclusions

These findings provided compelling evidence of the role of CIS in suppressing NPC metastasis and its underlying molecular mechanisms.
Literatur
1.
Zurück zum Zitat Cui Q, Feng FT, Xu M, Liu WS, Yao YY, Xie SH, Li XZ, Ye ZL, Feng QS, Chen LZ, Bei JX, Feng L, Huang QH, Jia WH, Cao SM, Chang ET, Ye W, Adami HO, Zeng YX (2016) Nasopharyngeal carcinoma risk prediction via salivary detection of host and Epstein–Barr virus genetic variants. Oncotarget. https://doi.org/10.18632/oncotarget.11144 Cui Q, Feng FT, Xu M, Liu WS, Yao YY, Xie SH, Li XZ, Ye ZL, Feng QS, Chen LZ, Bei JX, Feng L, Huang QH, Jia WH, Cao SM, Chang ET, Ye W, Adami HO, Zeng YX (2016) Nasopharyngeal carcinoma risk prediction via salivary detection of host and Epstein–Barr virus genetic variants. Oncotarget. https://​doi.​org/​10.​18632/​oncotarget.​11144
5.
Zurück zum Zitat Yao K, Yang S, Shen J, Zhang R, Li L (2016) HLA-DRB1 allele polymorphism and nasopharyngeal carcinoma risk: a meta-analysis. Eur Arch Oto-Rhino-Laryngol Off J Eur Fed Oto-Rhino-Laryngol Soc (EUFOS) Affil German Soc Oto-Rhino-Laryngol Head Neck Surg. https://doi.org/10.1007/s00405-016-4264-2 Yao K, Yang S, Shen J, Zhang R, Li L (2016) HLA-DRB1 allele polymorphism and nasopharyngeal carcinoma risk: a meta-analysis. Eur Arch Oto-Rhino-Laryngol Off J Eur Fed Oto-Rhino-Laryngol Soc (EUFOS) Affil German Soc Oto-Rhino-Laryngol Head Neck Surg. https://​doi.​org/​10.​1007/​s00405-016-4264-2
6.
Zurück zum Zitat Li JG, Venigalla P, Leeman JE, LaPlant Q, Setton J, Sherman E, Tsai J, McBride S, Riaz N, Lee N (2016) Patterns of nodal failure after intensity modulated radiotherapy for nasopharyngeal carcinoma. Laryngoscope. https://doi.org/10.1002/lary.26139 Li JG, Venigalla P, Leeman JE, LaPlant Q, Setton J, Sherman E, Tsai J, McBride S, Riaz N, Lee N (2016) Patterns of nodal failure after intensity modulated radiotherapy for nasopharyngeal carcinoma. Laryngoscope. https://​doi.​org/​10.​1002/​lary.​26139
8.
Zurück zum Zitat Ngan R, Yiu H, Lau W, Yau S, Cheung F, Chan T, Kwok C, Chiu C, Au S, Foo W (2002) Combination gemcitabine and cisplatin chemotherapy for metastatic or recurrent nasopharyngeal carcinoma: report of a phase II study. Ann Oncol 13(8):1252–1258CrossRefPubMed Ngan R, Yiu H, Lau W, Yau S, Cheung F, Chan T, Kwok C, Chiu C, Au S, Foo W (2002) Combination gemcitabine and cisplatin chemotherapy for metastatic or recurrent nasopharyngeal carcinoma: report of a phase II study. Ann Oncol 13(8):1252–1258CrossRefPubMed
9.
Zurück zum Zitat Group INCS., Trial VI (1996) Preliminary results of a randomized trial comparing neoadjuvant chemotherapy (cisplatin, epirubicin, bleomycin) plus radiotherapy vs. radiotherapy alone in stage IV (≥ N2, M0) undifferentiated nasopharyngeal carcinoma: a positive effect on progression-free survival. Int J Radiat Oncol Biol Phys 35(3):463–469CrossRef Group INCS., Trial VI (1996) Preliminary results of a randomized trial comparing neoadjuvant chemotherapy (cisplatin, epirubicin, bleomycin) plus radiotherapy vs. radiotherapy alone in stage IV (≥ N2, M0) undifferentiated nasopharyngeal carcinoma: a positive effect on progression-free survival. Int J Radiat Oncol Biol Phys 35(3):463–469CrossRef
10.
Zurück zum Zitat Chan AT, Leung S, Ngan RK, Teo PM, Lau W, Kwan W, Hui EP, Yiu H, Yeo W, Cheung F (2005) Overall survival after concurrent cisplatin–radiotherapy compared with radiotherapy alone in locoregionally advanced nasopharyngeal carcinoma. J Natl Cancer Inst 97(7):536–539CrossRefPubMed Chan AT, Leung S, Ngan RK, Teo PM, Lau W, Kwan W, Hui EP, Yiu H, Yeo W, Cheung F (2005) Overall survival after concurrent cisplatin–radiotherapy compared with radiotherapy alone in locoregionally advanced nasopharyngeal carcinoma. J Natl Cancer Inst 97(7):536–539CrossRefPubMed
11.
Zurück zum Zitat Rosanò L, Spinella F, Bagnato A (2013) Endothelin 1 in cancer: biological implications and therapeutic opportunities. Nat Rev Cancer 13(9):637–651CrossRefPubMed Rosanò L, Spinella F, Bagnato A (2013) Endothelin 1 in cancer: biological implications and therapeutic opportunities. Nat Rev Cancer 13(9):637–651CrossRefPubMed
12.
Zurück zum Zitat Lin SX, Zhang Y, Lu J, Liu X, Li XP (2016) Silencing of endothelin-1 suppresses growth, migration, and invasion of nasopharyngeal carcinoma cells in vitro. J Southern Med Univ 36(7):915–920 Lin SX, Zhang Y, Lu J, Liu X, Li XP (2016) Silencing of endothelin-1 suppresses growth, migration, and invasion of nasopharyngeal carcinoma cells in vitro. J Southern Med Univ 36(7):915–920
13.
Zurück zum Zitat McKenzie GA, Hinsley EE, Hunter K, Lambert DW (2014) The endothelin axis in head and neck cancer: a promising therapeutic opportunity? J Oral Pathol Med 43(6):395–404CrossRefPubMed McKenzie GA, Hinsley EE, Hunter K, Lambert DW (2014) The endothelin axis in head and neck cancer: a promising therapeutic opportunity? J Oral Pathol Med 43(6):395–404CrossRefPubMed
14.
Zurück zum Zitat Mai HQ, Zeng ZY, Feng KT, Ye YL, Zhang CQ, Liang WJ, Guo X, Mo HY, Hong MH (2006) Therapeutic targeting of the endothelin a receptor in human nasopharyngeal carcinoma. Cancer Sci 97(12):1388–1395CrossRefPubMed Mai HQ, Zeng ZY, Feng KT, Ye YL, Zhang CQ, Liang WJ, Guo X, Mo HY, Hong MH (2006) Therapeutic targeting of the endothelin a receptor in human nasopharyngeal carcinoma. Cancer Sci 97(12):1388–1395CrossRefPubMed
15.
Zurück zum Zitat Zheng H-c, Li J, Shen D-f, Yang X-f, Zhao S, Wu Y-z, Takano Y, Sun H-z, Su R-J, Luo J-S (2015) BTG1 expression correlates with pathogenesis, aggressive behaviors and prognosis of gastric cancer: a potential target for gene therapy. Oncotarget 6 (23):19685CrossRefPubMedPubMedCentral Zheng H-c, Li J, Shen D-f, Yang X-f, Zhao S, Wu Y-z, Takano Y, Sun H-z, Su R-J, Luo J-S (2015) BTG1 expression correlates with pathogenesis, aggressive behaviors and prognosis of gastric cancer: a potential target for gene therapy. Oncotarget 6 (23):19685CrossRefPubMedPubMedCentral
16.
Zurück zum Zitat Nahta R, Yuan LX, Fiterman DJ, Zhang L, Symmans WF, Ueno NT, Esteva FJ (2006) B cell translocation gene 1 contributes to antisense Bcl-2-mediated apoptosis in breast cancer cells. Mol Cancer Ther 5(6):1593–1601CrossRefPubMed Nahta R, Yuan LX, Fiterman DJ, Zhang L, Symmans WF, Ueno NT, Esteva FJ (2006) B cell translocation gene 1 contributes to antisense Bcl-2-mediated apoptosis in breast cancer cells. Mol Cancer Ther 5(6):1593–1601CrossRefPubMed
17.
Zurück zum Zitat Cho JW, Kim JJ, Park SG, Lee DH, Lee SC, Kim HJ, Park BC, Cho S (2004) Identification of B-cell translocation gene 1 as a biomarker for monitoring the remission of acute myeloid leukemia. Proteomics 4(11):3456–3463CrossRefPubMed Cho JW, Kim JJ, Park SG, Lee DH, Lee SC, Kim HJ, Park BC, Cho S (2004) Identification of B-cell translocation gene 1 as a biomarker for monitoring the remission of acute myeloid leukemia. Proteomics 4(11):3456–3463CrossRefPubMed
18.
Zurück zum Zitat Sun G, Wang Y, Cheng Y, Hu W (2014) The expression of BTG1 is downregulated in nasopharyngeal carcinoma and possibly associated with tumour metastasis. Mol Biol Rep 41(9):5979–5988CrossRefPubMed Sun G, Wang Y, Cheng Y, Hu W (2014) The expression of BTG1 is downregulated in nasopharyngeal carcinoma and possibly associated with tumour metastasis. Mol Biol Rep 41(9):5979–5988CrossRefPubMed
19.
Zurück zum Zitat Florea A-M, Büsselberg D (2011) Cisplatin as an anti-tumor drug: cellular mechanisms of activity, drug resistance and induced side effects. Cancers 3(1):1351–1371CrossRefPubMedPubMedCentral Florea A-M, Büsselberg D (2011) Cisplatin as an anti-tumor drug: cellular mechanisms of activity, drug resistance and induced side effects. Cancers 3(1):1351–1371CrossRefPubMedPubMedCentral
20.
Zurück zum Zitat Fuertes MA, Alonso C, Pérez JM (2003) Biochemical modulation of cisplatin mechanisms of action: enhancement of antitumor activity and circumvention of drug resistance. Chem Rev 103(3):645–662CrossRefPubMed Fuertes MA, Alonso C, Pérez JM (2003) Biochemical modulation of cisplatin mechanisms of action: enhancement of antitumor activity and circumvention of drug resistance. Chem Rev 103(3):645–662CrossRefPubMed
21.
Zurück zum Zitat Rusch V, Klimstra D, Venkatraman E, Oliver J, Martini N, Gralla R, Kris M, Dmitrovsky E (1995) Aberrant p53 expression predicts clinical resistance to cisplatin-based chemotherapy in locally advanced non-small cell lung cancer. Can Res 55(21):5038–5042 Rusch V, Klimstra D, Venkatraman E, Oliver J, Martini N, Gralla R, Kris M, Dmitrovsky E (1995) Aberrant p53 expression predicts clinical resistance to cisplatin-based chemotherapy in locally advanced non-small cell lung cancer. Can Res 55(21):5038–5042
22.
Zurück zum Zitat Godwin AK, Meister A, O’Dwyer PJ, Huang CS, Hamilton TC, Anderson ME (1992) High resistance to cisplatin in human ovarian cancer cell lines is associated with marked increase of glutathione synthesis. Proc Natl Acad Sci 89(7):3070–3074CrossRefPubMedPubMedCentral Godwin AK, Meister A, O’Dwyer PJ, Huang CS, Hamilton TC, Anderson ME (1992) High resistance to cisplatin in human ovarian cancer cell lines is associated with marked increase of glutathione synthesis. Proc Natl Acad Sci 89(7):3070–3074CrossRefPubMedPubMedCentral
23.
Zurück zum Zitat Sun X-J, Zhang P, Li H-H, Jiang Z-W, Jiang C-C, Liu H (2013) Cisplatin combined with metformin inhibits migration and invasion of human nasopharyngeal carcinoma cells by regulating E-cadherin and MMP-9. APJCP 15(9):4019–4023 Sun X-J, Zhang P, Li H-H, Jiang Z-W, Jiang C-C, Liu H (2013) Cisplatin combined with metformin inhibits migration and invasion of human nasopharyngeal carcinoma cells by regulating E-cadherin and MMP-9. APJCP 15(9):4019–4023
24.
Zurück zum Zitat Li M, Balch C, Montgomery JS, Jeong M, Chung JH, Yan P, Huang TH, Kim S, Nephew KP (2009) Integrated analysis of DNA methylation and gene expression reveals specific signaling pathways associated with platinum resistance in ovarian cancer. BMC Med Genom 2:34. https://doi.org/10.1186/1755-8794-2-34 CrossRef Li M, Balch C, Montgomery JS, Jeong M, Chung JH, Yan P, Huang TH, Kim S, Nephew KP (2009) Integrated analysis of DNA methylation and gene expression reveals specific signaling pathways associated with platinum resistance in ovarian cancer. BMC Med Genom 2:34. https://​doi.​org/​10.​1186/​1755-8794-2-34 CrossRef
29.
Zurück zum Zitat Hovanes K, Li TW, Munguia JE, Truong T, Milovanovic T, Lawrence Marsh J, Holcombe RF, Waterman ML (2001) Beta-catenin-sensitive isoforms of lymphoid enhancer factor-1 are selectively expressed in colon cancer. Nat Genet 28(1):53–57. https://doi.org/10.1038/88264 PubMed Hovanes K, Li TW, Munguia JE, Truong T, Milovanovic T, Lawrence Marsh J, Holcombe RF, Waterman ML (2001) Beta-catenin-sensitive isoforms of lymphoid enhancer factor-1 are selectively expressed in colon cancer. Nat Genet 28(1):53–57. https://​doi.​org/​10.​1038/​88264 PubMed
33.
Zurück zum Zitat Han X, Zhen S, Ye Z, Lu J, Wang L, Li P, Li J, Zheng X, Li H, Chen W, Zhao L, Li X (2017) A feedback loop between miR-30a/c-5p and DNMT1 mediates cisplatin resistance in ovarian cancer cells. Cell Physiol Biochem Int J Exp Cell Physiol Biochem Pharmacol. 41 (3):973–986. https://doi.org/10.1159/000460618 Han X, Zhen S, Ye Z, Lu J, Wang L, Li P, Li J, Zheng X, Li H, Chen W, Zhao L, Li X (2017) A feedback loop between miR-30a/c-5p and DNMT1 mediates cisplatin resistance in ovarian cancer cells. Cell Physiol Biochem Int J Exp Cell Physiol Biochem Pharmacol. 41 (3):973–986. https://​doi.​org/​10.​1159/​000460618
37.
Zurück zum Zitat Jiang Y, Wei YQ, Luo F, Zou LQ, Liu JY, Peng F, Huang MJ, He QM (2005) Gemcitabine and cisplatin in advanced nasopharyngeal carcinoma: a pilot study. Cancer Investig 23(2):123–128CrossRef Jiang Y, Wei YQ, Luo F, Zou LQ, Liu JY, Peng F, Huang MJ, He QM (2005) Gemcitabine and cisplatin in advanced nasopharyngeal carcinoma: a pilot study. Cancer Investig 23(2):123–128CrossRef
38.
Zurück zum Zitat Li P, Yang X, Cheng Y, Zhang X, Yang C, Deng X, Li P, Tao J, Yang H, Wei J, Tang J, Yuan W, Lu Q, Xu X, Gu M (2017) MicroRNA-218 increases the sensitivity of bladder cancer to cisplatin by targeting Glut1. Cell Physiol Biochem Int J Exp Cell Physiol Biochem Pharmacol 41(3):921–932. https://doi.org/10.1159/000460505 Li P, Yang X, Cheng Y, Zhang X, Yang C, Deng X, Li P, Tao J, Yang H, Wei J, Tang J, Yuan W, Lu Q, Xu X, Gu M (2017) MicroRNA-218 increases the sensitivity of bladder cancer to cisplatin by targeting Glut1. Cell Physiol Biochem Int J Exp Cell Physiol Biochem Pharmacol 41(3):921–932. https://​doi.​org/​10.​1159/​000460505
41.
Zurück zum Zitat Stewart CA, Tong P, Cardnell RJ, Sen T, Li L, Gay CM, Masrorpour F, Fan Y, Bara RO, Feng Y, Ru Y, Fujimoto J, Kundu ST, Post LE, Yu K, Shen Y, Glisson BS, Wistuba I, Heymach JV, Gibbons DL, Wang J, Byers LA (2017) Dynamic variations in epithelial-to-mesenchymal transition (EMT), ATM, and SLFN11 govern response to PARP inhibitors and cisplatin in small cell lung cancer. Oncotarget. https://doi.org/10.18632/oncotarget.15338 Stewart CA, Tong P, Cardnell RJ, Sen T, Li L, Gay CM, Masrorpour F, Fan Y, Bara RO, Feng Y, Ru Y, Fujimoto J, Kundu ST, Post LE, Yu K, Shen Y, Glisson BS, Wistuba I, Heymach JV, Gibbons DL, Wang J, Byers LA (2017) Dynamic variations in epithelial-to-mesenchymal transition (EMT), ATM, and SLFN11 govern response to PARP inhibitors and cisplatin in small cell lung cancer. Oncotarget. https://​doi.​org/​10.​18632/​oncotarget.​15338
42.
50.
Zurück zum Zitat Del Bufalo D, Di Castro V, Biroccio A, Varmi M, Salani D, Rosano L, Trisciuoglio D, Spinella F, Bagnato A (2002) Endothelin-1 protects ovarian carcinoma cells against paclitaxel-induced apoptosis: requirement for Akt activation. Mol Pharmacol 61(3):524–532CrossRefPubMed Del Bufalo D, Di Castro V, Biroccio A, Varmi M, Salani D, Rosano L, Trisciuoglio D, Spinella F, Bagnato A (2002) Endothelin-1 protects ovarian carcinoma cells against paclitaxel-induced apoptosis: requirement for Akt activation. Mol Pharmacol 61(3):524–532CrossRefPubMed
Metadaten
Titel
Cisplatin suppresses proliferation, migration and invasion of nasopharyngeal carcinoma cells in vitro by repressing the Wnt/β-catenin/Endothelin-1 axis via activating B cell translocation gene 1
verfasst von
Peng Yin
Guizhen Song
Zhenhua Jiang
Publikationsdatum
14.03.2018
Verlag
Springer Berlin Heidelberg
Erschienen in
Cancer Chemotherapy and Pharmacology / Ausgabe 5/2018
Print ISSN: 0344-5704
Elektronische ISSN: 1432-0843
DOI
https://doi.org/10.1007/s00280-018-3536-5

Weitere Artikel der Ausgabe 5/2018

Cancer Chemotherapy and Pharmacology 5/2018 Zur Ausgabe

Wo hapert es noch bei der Umsetzung der POMGAT-Leitlinie?

03.05.2024 DCK 2024 Kongressbericht

Seit November 2023 gibt es evidenzbasierte Empfehlungen zum perioperativen Management bei gastrointestinalen Tumoren (POMGAT) auf S3-Niveau. Vieles wird schon entsprechend der Empfehlungen durchgeführt. Wo es im Alltag noch hapert, zeigt eine Umfrage in einem Klinikverbund.

Bestrahlung nach Prostatektomie: mehr Schaden als Nutzen?

02.05.2024 Prostatakarzinom Nachrichten

Eine adjuvante Radiotherapie nach radikaler Prostata-Op. bringt den Betroffenen wahrscheinlich keinen Vorteil. Im Gegenteil: Durch die Bestrahlung steigt offenbar das Risiko für Harn- und Stuhlinkontinenz.

ASS schützt nicht vor Brustkrebsrezidiven

02.05.2024 Mammakarzinom Nachrichten

Nützt nichts und ist vielleicht sogar schädlich: In einer Phase-3-Studie konnten täglich 300 mg ASS keine Brustkrebsrezidive bei Frauen vermeiden, die ein hohes Risiko für eine Tumorrückkehr aufwiesen. Tendenziell traten unter ASS sogar häufiger Rezidive auf als unter Placebo.

CUP-Syndrom: Künstliche Intelligenz kann Primärtumor finden

30.04.2024 Künstliche Intelligenz Nachrichten

Krebserkrankungen unbekannten Ursprungs (CUP) sind eine diagnostische Herausforderung. KI-Systeme können Pathologen dabei unterstützen, zytologische Bilder zu interpretieren, um den Primärtumor zu lokalisieren.

Update Onkologie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.