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Chloroquine promotes gefitinib‑induced apoptosis by inhibiting protective autophagy in cutaneous squamous cell carcinoma

  • Authors:
    • Chengshan Ou
    • Hongxia Liu
    • Zhenhua Ding
    • Liang Zhou
  • View Affiliations / Copyright

    Affiliations: Department of Radiation Medicine, Guangdong Provincial Key Laboratory of Tropical Disease Research, School of Public Health, Southern Medical University, Guangzhou, Guangdong 510515, P.R. China, Department of Toxicology, Guangdong Provincial Key Laboratory of Tropical Disease Research, School of Public Health, Southern Medical University, Guangzhou, Guangdong 510515, P.R. China
    Copyright: © Ou et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Pages: 4855-4866
    |
    Published online on: October 9, 2019
       https://doi.org/10.3892/mmr.2019.10734
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Abstract

Aberrant expression of the epidermal growth factor receptor (EGFR) plays vital roles in tumor development and progression. In the present study, ultraviolet irradiation induced the upregulation of EGFR in skin‑derived keratinocytes, which may contribute to the development of cutaneous squamous cell carcinoma (CSCC). This was supported by the high expression of EGFR in CSCC clinical samples. Treating A431 CSCC cells with gefitinib, a tyrosine kinase inhibitor, activated the intrinsic mitochondrial apoptotic pathway while inducing protective autophagy. Combined application of chloroquine with gefitinib enhanced the treatment efficacy of gefitinib against CSCC by inhibiting autophagic flux. These findings demonstrated that autophagy inhibition may be an effective strategy for enhancing the sensitivity of EGFR‑expressing cells to tyrosine kinase inhibitor treatment. Manipulating pro‑survival autophagy by the combined application of chloroquine with gefitinib is a promising approach for improving the efficacy of EGFR inhibitors in cancer treatment. This may contribute to novel EGFR‑targeted therapeutic strategies in the near future.
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1 

Lomas A, Leonardi-Bee J and Bath-Hextall F: A systematic review of worldwide incidence of nonmelanoma skin cancer. Br J Dermatol. 166:1069–1080. 2012. View Article : Google Scholar : PubMed/NCBI

2 

El-Abaseri TB, Fuhrman J, Trempus C, Shendrik I, Tennant RW and Hansen LA: Chemoprevention of UV light-induced skin tumorigenesis by inhibition of the epidermal growth factor receptor. Cancer Res. 65:3958–3965. 2005. View Article : Google Scholar : PubMed/NCBI

3 

Kyriakis JM and Avruch J: Protein kinase cascades activated by stress and inflammatory cytokines. Bioessays. 18:567–577. 1996. View Article : Google Scholar : PubMed/NCBI

4 

Rosette C and Karin M: Ultraviolet light and osmotic stress: Activation of the JNK cascade through multiple growth factor and cytokine receptors. Science. 274:1194–1197. 1996. View Article : Google Scholar : PubMed/NCBI

5 

Lewis CM, Glisson BS, Feng L, Wan F, Tang X, Wistuba II, El-Naggar AK, Rosenthal DI, Chambers MS, Lustig RA and Weber RS: A phase II study of gefitinib for aggressive cutaneous squamous cell carcinoma of the head and neck. Clin Cancer Res. 18:1435–1446. 2012. View Article : Google Scholar : PubMed/NCBI

6 

Alam M and Ratner D: Cutaneous squamous-cell carcinoma. N Engl J Med. 344:975–983. 2001. View Article : Google Scholar : PubMed/NCBI

7 

Chang CY, Kuan YH, Ou YC, Li JR, Wu CC, Pan PH, Chen WY, Huang HY and Chen CJ: Autophagy contributes to gefitinib-induced glioma cell growth inhibition. Exp Cell Res. 327:102–112. 2014. View Article : Google Scholar : PubMed/NCBI

8 

Merlino GT, Xu YH, Ishii S, Clark AJ, Semba K, Toyoshima K, Yamamoto T and Pastan I: Amplification and enhanced expression of the epidermal growth factor receptor gene in A431 human carcinoma cells. Science. 224:417–419. 1984. View Article : Google Scholar : PubMed/NCBI

9 

Degenhardt K, Mathew R, Beaudoin B, Bray K, Anderson D, Chen G, Mukherjee C, Shi Y, Gélinas C, Fan Y, et al: Autophagy promotes tumor cell survival and restricts necrosis, inflammation, and tumorigenesis. Cancer Cell. 10:51–64. 2006. View Article : Google Scholar : PubMed/NCBI

10 

Yang ZJ, Chee CE, Huang S and Sinicrope FA: The role of autophagy in cancer: therapeutic implications. Mol Cancer Ther. 10:1533–1541. 2011. View Article : Google Scholar : PubMed/NCBI

11 

Klionsky DJ, Abdalla FC, Abeliovich H, Abraham RT, Acevedo-Arozena A, Adeli K, Agholme L, Agnello M, Agostinis P, Aguirre-Ghiso JA, et al: Guidelines for the use and interpretation of assays for monitoring autophagy. Autophagy. 8:445–544. 2012. View Article : Google Scholar : PubMed/NCBI

12 

Zhou L, Wang Y, Zhou M, Zhang Y, Wang P, Li X, Yang J, Wang H and Ding Z: HOXA9 inhibits HIF-1α-mediated glycolysis through interacting with CRIP2 to repress cutaneous squamous cell carcinoma development. Nat Commun. 9:14802018. View Article : Google Scholar : PubMed/NCBI

13 

Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) method. Methods. 25:402–408. 2001. View Article : Google Scholar : PubMed/NCBI

14 

Feoktistova M, Geserick P and Leverkus M: Crystal violet assay for determining viability of cultured cells. Cold Spring Harbor Protocols. 2016:pdb.prot087379. 2016. View Article : Google Scholar

15 

Thomé MP, Filippi-Chiela EC, Villodre ES, Migliavaca CB, Onzi GR, Felipe KB and Lenz G: Ratiometric analysis of acridine orange staining in the study of acidic organelles and autophagy. J Cell Sci. 129:4622–4632. 2016. View Article : Google Scholar : PubMed/NCBI

16 

Lynch TJ, Bell DW, Sordella R, Gurubhagavatula S, Okimoto RA, Brannigan BW, Harris PL, Haserlat SM, Supko JG, Haluska FG, et al: Activating mutations in the epidermal growth factor receptor underlying responsiveness of non-small-cell lung cancer to gefitinib. N Engl J Med. 350:2129–2139. 2004. View Article : Google Scholar : PubMed/NCBI

17 

Ciardiello F and Tortora G: EGFR antagonists in cancer treatment. N Engl J Med. 358:1160–1174. 2008. View Article : Google Scholar : PubMed/NCBI

18 

Johnston JB, Navaratnam S, Pitz MW, Maniate JM, Wiechec E, Baust H, Gingerich J, Skliris GP, Murphy LC and Los M: Targeting the EGFR pathway for cancer therapy. Curr Med Chem. 13:3483–3492. 2006. View Article : Google Scholar : PubMed/NCBI

19 

Bethune G, Bethune D, Ridgway N and Xu Z: Epidermal growth factor receptor (EGFR) in lung cancer: An overview and update. J Thorac Dis. 2:48–51. 2010.PubMed/NCBI

20 

Henson ES and Gibson SB: Surviving cell death through epidermal growth factor (EGF) signal transduction pathways: Implications for cancer therapy. Cell Signal. 18:2089–2097. 2006. View Article : Google Scholar : PubMed/NCBI

21 

Kobayashi S, Boggon TJ, Dayaram T, Jänne PA, Kocher O, Meyerson M, Johnson BE, Eck MJ, Tenen DG and Halmos B: EGFR mutation and resistance of non-small-cell lung cancer to gefitinib. N Engl J Med. 352:786–792. 2005. View Article : Google Scholar : PubMed/NCBI

22 

Galluzzi L, Aaronson SA, Abrams J, Alnemri ES, Andrews DW, Baehrecke EH, Bazan NG, Blagosklonny MV, Blomgren K, Borner C, et al: Guidelines for the use and interpretation of assays for monitoring cell death in higher eukaryotes. Cell Death Differ. 16:1093–1107. 2009. View Article : Google Scholar : PubMed/NCBI

23 

Galluzzi L, Pietrocola F, Amaravadi RK, Bravo-San Pedro JM, Amaravadi RK, Baehrecke EH, Cecconi F, Codogno P, Debnath J, Gewirtz DA, et al: Autophagy in malignant transformation and cancer progression. EMBO J. 34:856–880. 2015. View Article : Google Scholar : PubMed/NCBI

24 

Dragowska WH, Weppler SA, Wang JC, Wong LY, Kapanen AI, Rawji JS, Warburton C, Qadir MA, Donohue E, Roberge M, et al: Induction of autophagy is an early response to gefitinib and a potential therapeutic target in breast cancer. PLoS One. 8:e765032013. View Article : Google Scholar : PubMed/NCBI

25 

Masuelli L, Granato M, Benvenuto M, Mattera R, Bernardini R, Mattei M, d'Amati G, D'Orazi G, Faggioni A, Bei R and Cirone M: Chloroquine supplementation increases the cytotoxic effect of curcumin against Her2/neu overexpressing breast cancer cells in vitro and in vivo in nude mice while counteracts it in immune competent mice. Oncoimmunology. 6:e13561512017. View Article : Google Scholar : PubMed/NCBI

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Copy and paste a formatted citation
Spandidos Publications style
Ou C, Liu H, Ding Z and Zhou L: Chloroquine promotes gefitinib‑induced apoptosis by inhibiting protective autophagy in cutaneous squamous cell carcinoma. Mol Med Rep 20: 4855-4866, 2019.
APA
Ou, C., Liu, H., Ding, Z., & Zhou, L. (2019). Chloroquine promotes gefitinib‑induced apoptosis by inhibiting protective autophagy in cutaneous squamous cell carcinoma. Molecular Medicine Reports, 20, 4855-4866. https://doi.org/10.3892/mmr.2019.10734
MLA
Ou, C., Liu, H., Ding, Z., Zhou, L."Chloroquine promotes gefitinib‑induced apoptosis by inhibiting protective autophagy in cutaneous squamous cell carcinoma". Molecular Medicine Reports 20.6 (2019): 4855-4866.
Chicago
Ou, C., Liu, H., Ding, Z., Zhou, L."Chloroquine promotes gefitinib‑induced apoptosis by inhibiting protective autophagy in cutaneous squamous cell carcinoma". Molecular Medicine Reports 20, no. 6 (2019): 4855-4866. https://doi.org/10.3892/mmr.2019.10734
Copy and paste a formatted citation
x
Spandidos Publications style
Ou C, Liu H, Ding Z and Zhou L: Chloroquine promotes gefitinib‑induced apoptosis by inhibiting protective autophagy in cutaneous squamous cell carcinoma. Mol Med Rep 20: 4855-4866, 2019.
APA
Ou, C., Liu, H., Ding, Z., & Zhou, L. (2019). Chloroquine promotes gefitinib‑induced apoptosis by inhibiting protective autophagy in cutaneous squamous cell carcinoma. Molecular Medicine Reports, 20, 4855-4866. https://doi.org/10.3892/mmr.2019.10734
MLA
Ou, C., Liu, H., Ding, Z., Zhou, L."Chloroquine promotes gefitinib‑induced apoptosis by inhibiting protective autophagy in cutaneous squamous cell carcinoma". Molecular Medicine Reports 20.6 (2019): 4855-4866.
Chicago
Ou, C., Liu, H., Ding, Z., Zhou, L."Chloroquine promotes gefitinib‑induced apoptosis by inhibiting protective autophagy in cutaneous squamous cell carcinoma". Molecular Medicine Reports 20, no. 6 (2019): 4855-4866. https://doi.org/10.3892/mmr.2019.10734
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