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Article

Combination of FTY720 with cisplatin exhibits antagonistic effects in ovarian cancer cells: Role of autophagy

  • Authors:
    • Ning Zhang
    • Lan Dai
    • Yanfei Qi
    • Wen Di
    • Pu Xia
  • View Affiliations / Copyright

    Affiliations: Department of Obstetrics and Gynecology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, P.R. China, Signal Transduction Program, Centenary Institute, Sydney Medical School, University of Sydney, Australia
  • Pages: 2053-2059
    |
    Published online on: April 17, 2013
       https://doi.org/10.3892/ijo.2013.1906
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Abstract

Combination therapy with different anticancer drugs has been proven to be an effective strategy for the treatment of various types of cancers, including ovarian cancer. We have previously reported that FTY720 exhibited potent cytotoxic effects in ovarian cancer cells through the necrotic pathway, which differs from the killing effect of cisplatin (CDDP). In the present study, we report that the combination of FTY720 with CDDP yields an unexpected antagonistic effect towards the cytotoxicity of CDDP in a variety of ovarian cancer cell lines, including both CDDP-sensitive and -resistant cells. The antagonistic activity of FTY720 appears ascribable to its effect in autophagy induction. A significant increase in baseline autophagy was observed in CDDP-resistant ovarian cancer cells, compared with the sensitive cells. Blockade of autophagy by either a pharmacological inhibitor (3-MA) or siRNA-mediated knockdown of autophagic gene expression enhances CDDP-induced apoptotic cell death. Notably, by inhibiting autophagy, 3-MA can convert the combination of FTY720 with CDDP from an antagonistic into an additive effect towards killing ovarian cancer cells. Collectively, the findings suggest that a combination of an autophagy regulator with the CDDP-based regime could effectively modulate its efficacy for the treatment of ovarian cancer.
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1 

Jemal A, Siegel R, Ward E, Hao Y, Xu J and Thun MJ: Cancer statistics, 2009. CA Cancer J Clin. 59:225–249. 2009. View Article : Google Scholar

2 

Bast RC Jr, Hennessy B and Mills GB: The biology of ovarian cancer: new opportunities for translation. Nat Rev Cancer. 9:415–428. 2009. View Article : Google Scholar : PubMed/NCBI

3 

Shintani T and Klionsky DJ: Autophagy in health and disease: a double-edged sword. Science. 306:990–995. 2004. View Article : Google Scholar : PubMed/NCBI

4 

Levine B and Kroemer G: Autophagy in the pathogenesis of disease. Cell. 132:27–42. 2008. View Article : Google Scholar : PubMed/NCBI

5 

Mizushima N, Levine B, Cuervo AM and Klionsky DJ: Autophagy fights disease through cellular self-digestion. Nature. 451:1069–1075. 2008. View Article : Google Scholar : PubMed/NCBI

6 

Maiuri MC, Zalckvar E, Kimchi A and Kroemer G: Self-eating and self-killing: crosstalk between autophagy and apoptosis. Nat Rev Mol Cell Biol. 8:741–752. 2007. View Article : Google Scholar : PubMed/NCBI

7 

Kroemer G and Levine B: Autophagic cell death: the story of a misnomer. Nat Rev Mol Cell Biol. 9:1004–1010. 2008. View Article : Google Scholar : PubMed/NCBI

8 

Kondo Y, Kanzawa T, Sawaya R and Kondo S: The role of autophagy in cancer development and response to therapy. Nat Rev Cancer. 5:726–734. 2005. View Article : Google Scholar : PubMed/NCBI

9 

Suzuki S, Enosawa S, Kakefuda T, Shinomiya T, Amari M, Naoe S, Hoshino Y and Chiba K: A novel immunosuppressant, FTY720, with a unique mechanism of action, induces long-term graft acceptance in rat and dog allotransplantation. Transplantation. 61:200–205. 1996. View Article : Google Scholar : PubMed/NCBI

10 

Suzuki S, Enosawa S, Kakefuda T, Li XK, Mitsusada M, Takahara S and Amemiya H: Immunosuppressive effect of a new drug, FTY720, on lymphocyte responses in vitro and cardiac allograft survival in rats. Transpl Immunol. 4:252–455. 1996. View Article : Google Scholar : PubMed/NCBI

11 

Tedesco-Silva H, Mourad G, Kahan BD, Boira JG, Weimar W, Mulgaonkar S, Nashan B, Madsen S, Charpentier B, Pellet P and Vanrenterghem Y: FTY720, a novel immunomodulator: efficacy and safety results from the first phase 2A study in de novo renal transplantation. Transplantation. 77:1826–1833. 2004.PubMed/NCBI

12 

Pelletier D and Hafler DA: Fingolimod for multiple sclerosis. N Engl J Med. 366:339–347. 2012. View Article : Google Scholar

13 

Vadas M, Xia P, McCaughan G and Gamble J: The role of sphingosine kinase 1 in cancer: oncogene or non-oncogene addiction? Biochim Biophys Acta. 1781:442–447. 2008. View Article : Google Scholar : PubMed/NCBI

14 

Zhang N, Qi Y, Wadham C, Wang L, Warren A, Di W and Xia P: FTY720 induces necrotic cell death and autophagy in ovarian cancer cells: a protective role of autophagy. Autophagy. 6:1157–1167. 2010. View Article : Google Scholar : PubMed/NCBI

15 

Sukocheva O, Wang L, Verrier E, Vadas MA and Xia P: Restoring endocrine response in breast cancer cells by inhibition of the sphingosine kinase-1 signaling pathway. Endocrinology. 150:4484–4492. 2009. View Article : Google Scholar : PubMed/NCBI

16 

Chou TC and Talalay P: Quantitative analysis of dose-effect relationships: the combined effects of multiple drugs or enzyme inhibitors. Adv Enzyme Regul. 22:27–55. 1984. View Article : Google Scholar : PubMed/NCBI

17 

Chou TC: Theoretical basis, experimental design, and computerized simulation of synergism and antagonism in drug combination studies. Pharmacol Rev. 58:621–681. 2006. View Article : Google Scholar : PubMed/NCBI

18 

Zhang N, Wu ZM, McGowan E, Shi J, Hong ZB, Ding CW, Xia P and Di W: Arsenic trioxide and cisplatin synergism increase cytotoxicity in human ovarian cancer cells: therapeutic potential for ovarian cancer. Cancer Sci. 100:2459–2464. 2009. View Article : Google Scholar

19 

Agarwal R and Kaye SB: Ovarian cancer: strategies for overcoming resistance to chemotherapy. Nat Rev Cancer. 3:502–516. 2003. View Article : Google Scholar : PubMed/NCBI

20 

Muggia F: Platinum compounds 30 years after the introduction of cisplatin: implications for the treatment of ovarian cancer. Gynecol Oncol. 112:275–281. 2009.PubMed/NCBI

21 

Seglen PO and Gordon PB: 3-Methyladenine: specific inhibitor of autophagic/lysosomal protein degradation in isolated rat hepatocytes. Proc Natl Acad Sci USA. 79:1889–1892. 1982. View Article : Google Scholar : PubMed/NCBI

22 

Tassa A, Roux MP, Attaix D and Bechet DM: Class III phosphoinositide 3-kinase - Beclin1 complex mediates the amino acid-dependent regulation of autophagy in C2C12 myotubes. Biochem J. 376:577–586. 2003. View Article : Google Scholar : PubMed/NCBI

23 

Alinari L, Mahoney E, Patton J, Zhang X, Huynh L, Earl CT, Mani R, Mao Y, Yu B, Quinion C, Towns WH, Chen CS, Goldenberg DM, Blum KA, Byrd JC, Muthusamy N, Praetorius-Ibba M and Baiocchi RA: FTY720 increases CD74 expression and sensitizes mantle cell lymphoma cells to milatuzumab-mediated cell death. Blood. 118:6893–6903. 2011. View Article : Google Scholar : PubMed/NCBI

24 

Romero Rosales K, Singh G, Wu K, Chen J, Janes MR, Lilly MB, Peralta ER, Siskind LJ, Bennett MJ, Fruman DA and Edinger AL: Sphingolipid-based drugs selectively kill cancer cells by down-regulating nutrient transporter proteins. Biochem J. 439:299–311. 2011.PubMed/NCBI

25 

Wallington-Beddoe CT, Hewson J, Bradstock KF and Bendall LJ: FTY720 produces caspase-independent cell death of acute lymphoblastic leukemia cells. Autophagy. 7:707–715. 2011. View Article : Google Scholar : PubMed/NCBI

26 

Liao A, Hu R, Zhao Q, Li J, Li Y, Yao K, Zhang R, Wang H, Yang W and Liu Z: Autophagy induced by FTY720 promotes apoptosis in U266 cells. Eur J Pharm Sci. 45:600–605. 2012. View Article : Google Scholar : PubMed/NCBI

27 

Paglin S, Hollister T, Delohery T, Hackett N, McMahill M, Sphicas E, Domingo D and Yahalom J: A novel response of cancer cells to radiation involves autophagy and formation of acidic vesicles. Cancer Res. 61:439–444. 2001.

28 

Kanzawa T, Germano IM, Komata T, Ito H, Kondo Y and Kondo S: Role of autophagy in temozolomide-induced cytotoxicity for malignant glioma cells. Cell Death Differ. 11:448–457. 2004. View Article : Google Scholar : PubMed/NCBI

29 

Sato K, Tsuchihara K, Fujii S, Sugiyama M, Goya T, Atomi Y, Ueno T, Ochiai A and Esumi H: Autophagy is activated in colorectal cancer cells and contributes to the tolerance to nutrient deprivation. Cancer Res. 67:9677–9684. 2007. View Article : Google Scholar : PubMed/NCBI

30 

Amaravadi RK, Yu D, Lum JJ, Bui T, Christophorou MA, Evan GI, Thomas-Tikhonenko A and Thompson CB: Autophagy inhibition enhances therapy-induced apoptosis in a Myc-induced model of lymphoma. J Clin Invest. 117:326–336. 2007. View Article : Google Scholar : PubMed/NCBI

31 

Apel A, Herr I, Schwarz H, Rodemann HP and Mayer A: Blocked autophagy sensitizes resistant carcinoma cells to radiation therapy. Cancer Res. 68:1485–1494. 2008. View Article : Google Scholar : PubMed/NCBI

32 

Bellodi C, Lidonnici MR, Hamilton A, Helgason GV, Soliera AR, Ronchetti M, Galavotti S, Young KW, Selmi T, Yacobi R, Van Etten RA, Donato N, Hunter A, Dinsdale D, Tirrò E, Vigneri P, Nicotera P, Dyer MJ, Holyoake T, Salomoni P and Calabretta B: Targeting autophagy potentiates tyrosine kinase inhibitor-induced cell death in Philadelphia chromosome-positive cells, including primary CML stem cells. J Clin Invest. 119:1109–1123. 2009. View Article : Google Scholar

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Copy and paste a formatted citation
Spandidos Publications style
Zhang N, Dai L, Qi Y, Di W and Xia P: Combination of FTY720 with cisplatin exhibits antagonistic effects in ovarian cancer cells: Role of autophagy. Int J Oncol 42: 2053-2059, 2013.
APA
Zhang, N., Dai, L., Qi, Y., Di, W., & Xia, P. (2013). Combination of FTY720 with cisplatin exhibits antagonistic effects in ovarian cancer cells: Role of autophagy. International Journal of Oncology, 42, 2053-2059. https://doi.org/10.3892/ijo.2013.1906
MLA
Zhang, N., Dai, L., Qi, Y., Di, W., Xia, P."Combination of FTY720 with cisplatin exhibits antagonistic effects in ovarian cancer cells: Role of autophagy". International Journal of Oncology 42.6 (2013): 2053-2059.
Chicago
Zhang, N., Dai, L., Qi, Y., Di, W., Xia, P."Combination of FTY720 with cisplatin exhibits antagonistic effects in ovarian cancer cells: Role of autophagy". International Journal of Oncology 42, no. 6 (2013): 2053-2059. https://doi.org/10.3892/ijo.2013.1906
Copy and paste a formatted citation
x
Spandidos Publications style
Zhang N, Dai L, Qi Y, Di W and Xia P: Combination of FTY720 with cisplatin exhibits antagonistic effects in ovarian cancer cells: Role of autophagy. Int J Oncol 42: 2053-2059, 2013.
APA
Zhang, N., Dai, L., Qi, Y., Di, W., & Xia, P. (2013). Combination of FTY720 with cisplatin exhibits antagonistic effects in ovarian cancer cells: Role of autophagy. International Journal of Oncology, 42, 2053-2059. https://doi.org/10.3892/ijo.2013.1906
MLA
Zhang, N., Dai, L., Qi, Y., Di, W., Xia, P."Combination of FTY720 with cisplatin exhibits antagonistic effects in ovarian cancer cells: Role of autophagy". International Journal of Oncology 42.6 (2013): 2053-2059.
Chicago
Zhang, N., Dai, L., Qi, Y., Di, W., Xia, P."Combination of FTY720 with cisplatin exhibits antagonistic effects in ovarian cancer cells: Role of autophagy". International Journal of Oncology 42, no. 6 (2013): 2053-2059. https://doi.org/10.3892/ijo.2013.1906
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