DOI QR코드

DOI QR Code

AZD1480 Can Inhibit the Biological Behavior of Ovarian Cancer SKOV3 Cells in vitro

  • Sun, Zhao-Ling (Department of Gynecology and Obstetrics, HeBei United University Affiliated Hospital) ;
  • Tang, Ya-Juan (Department of Gynecology and Obstetrics, HeBei United University Affiliated Hospital) ;
  • Wu, Wei-Guang (Department of Gynecology and Obstetrics, HeBei United University Affiliated Hospital) ;
  • Xing, Jun (Department of Gynecology and Obstetrics, HeBei United University Affiliated Hospital) ;
  • He, Yan-Fang (Department of Gynecology and Obstetrics, HeBei United University Affiliated Hospital) ;
  • Xin, De-Mei (Department of Gynecology and Obstetrics, HeBei United University Affiliated Hospital) ;
  • Yu, Yan-Li (Department of Gynecology and Obstetrics, HeBei United University Affiliated Hospital) ;
  • Yang, Yang (Department of Gynecology and Obstetrics, HeBei United University Affiliated Hospital) ;
  • Han, Ping (Department of Gynecology and Obstetrics, HeBei United University Affiliated Hospital)
  • Published : 2013.08.30

Abstract

Objective: To study the mechanism of effects of AZD1480 on the SKOV3 ovarian cancer cell line. Methods: The MTT method was used to assess cellular proliferation, flow cytometry for cellular apoptosis, the scratch test to determine migration, transwell chamber assays to detect cellular invasion, plate clone experiments to detect the clone forming ability and Western blotting to determine p-STAT3 protein levels. Results: The proliferation rate, migration ability, invasiveness and the clone forming ability of SKOV3 cells were reduced after treatment with AZD1480, while apoptosis rate and chemotherapeutic susceptibility were increased. After treatment with AZD1480 plus cisplatin, the apoptosis rate increased significantly while the expression level of p-STAT3 protein was decreased. Conclusion: AZD1480 can inhibit the proliferation, invasion, metastasis and clone formation of SKOV3 cells, induce cellulsar apoptosis, increase the chemotherapeutic sensitivity and reduce the expression level of p-STAT3 protein.

Keywords

SKOV3 cells;JAK inhibitor;AZD1480;biological behavior;p-STAT3

References

  1. Alberts DS, Hannigan EV, Liu PY, et a1 (2006). Randomized trial of adjuvant intraperitoneal alpha-interferon in stage III ovarian cancer patients who have no evidence of disease after primary surgery and chemotherapy: An intergroup study. Gynecol Oncol, 100, 133-8. https://doi.org/10.1016/j.ygyno.2005.07.117
  2. Bid HK, Oswald D, Li C, et al (2012). Anti-Angiogenic Activity of a Small Molecule STAT3 Inhibitor LLL12. PLoS One, 7, e35513. https://doi.org/10.1371/journal.pone.0035513
  3. Bromberg JF, Wrzeszczynska MH, Devgan G, et al (1999). STAT3 as an oncogene. Cell, 98, 295-303. https://doi.org/10.1016/S0092-8674(00)81959-5
  4. Couto JP, Almeida A, Daly L, et al (2012). AZD1480 Blocks Growth and Tumorigenesis of RET- Activated Thyroid Cancer Cell Lines. PLoS One, 7, e46869. https://doi.org/10.1371/journal.pone.0046869
  5. de Groot J, Liang J, Kong LY, et al (2012). Modulating Antiangiogenic Resistance by Inhibiting the Signal Transducer and Activator of Transcription 3 Pathway in Glioblastoma. Oncotarget, 3, 1036-48.
  6. Guo W, Wu S, Wang L, et al (2011). Antitumor activity of a novel oncrasin analogue is mediated by JNK activation and STAT3 inhibition. PLoS One, 6, e28487. https://doi.org/10.1371/journal.pone.0028487
  7. Hedvat M, Huszar D, Herrmann A, et al (2009). The JAK2 inhibitor AZD1480 potently blocks Stat3 signaling and oncogenesis in solid tumors. Cancer Cell, 16, 487-97. https://doi.org/10.1016/j.ccr.2009.10.015
  8. Jing N, Li Y, Xiong W, et al (2004). G-quartet oligonucleotides: a new class of signal transducer and activator of transcription 3 inhibitors that suppresses growth of prostate and breast tumors through induction of apoptosis. Cancer Res, 64, 6603-9. https://doi.org/10.1158/0008-5472.CAN-03-4041
  9. Kandala PK, Srivastava SK (2012). Regulation of Janus-activated kinase-2 (JAK2) by diindolylmethane in ovarian cancer in vitro and in vivo. Drug Discov Ther, 6, 94-101.
  10. Lai SY, Johnson FM (2010). Defining the role of the JAK-STAT pathway in head and neck and thoracic malignancies: implications for future therapeutic approaches. Clini Drug Resist Updat, 13, 67-78. https://doi.org/10.1016/j.drup.2010.04.001
  11. Leong P L, Andrews G A, Johnson D E, et a1(2003). Targeted inhibition of Stat3 with a decoy oligonucleotide abrogates head and neck cancer cell growth. Proc Natl Acad Sci USA, 100, 4138-43. https://doi.org/10.1073/pnas.0534764100
  12. Loveless ME, Lawson D, Collins M, et al (2012). Comparisons of the efficacy of a Jak1/2 inhibitor (AZD1480) with a VEGF signaling inhibitor (cediranib) and sham treatments in mouse tumors using DCE-MRI, DW-MRI, and histology.Neoplasia, 14, 54-64.
  13. McFarland BC, Ma JY, Langford CP, et al (2011). Therapeutic potential of AZD1480 for the treatment of human glioblastoma. Mol Cancer Ther, 10, 2384-93. https://doi.org/10.1158/1535-7163.MCT-11-0480
  14. Monk BJ, Tewari KS, Koh WJ(2007). Multimodality therapy for locally advanced cervical carcinoma: state of the art and future directions. J Clin Oncol, 25, 2952-65. https://doi.org/10.1200/JCO.2007.10.8324
  15. Piccart MJ, Bertelsen K, Stuart G, et a1 (2003). Long-term follow-up confirms a survival advantage of the paclitaxel-cisplatin regimen over the cyclophosphamide-cisplatin combination in advanced ovarian cancer. Int J Gynecol Cancer, 13,144-8. https://doi.org/10.1111/j.1525-1438.2003.13357.x
  16. Ptak A, Gregoraszczuk EL (2012). Bisphenol A induces leptin receptor expression, creating more binding sites for leptin, and activates theJAK/Stat, MAPK/ERK and PI3K/Akt signalling pathways in human ovarian cancer cell. Toxicol Lett, 210, 332-7. https://doi.org/10.1016/j.toxlet.2012.02.003
  17. Scuto A, Krejci P, Popplewell L, et al (2011). The novel JAK inhibitor AZD1480 blocks STAT3 and FGFR3 signaling, resulting in suppression of human myeloma cell growth and survival. Leukemia, 25, 538-50 https://doi.org/10.1038/leu.2010.289
  18. Shin DS, Kim HN, Shin KD, et al (2009). Cryptotanshinone inhibits constitutive signal transducer and activator of transcription 3 function through blocking the dimerization in DU145 prostate cancer cells. Cancer Res, 69, 193-202. https://doi.org/10.1158/0008-5472.CAN-08-2575
  19. Shirali S, Aghaei M, Shabani M, et al (2013). Adenosine induces cell cycle arrest and apoptosis via cyclinD1/Cdk4 and Bcl-2/Bax pathways in humanovarian cancer cell line OVCAR-3. Tumour Biol, 34, 1085-95. https://doi.org/10.1007/s13277-013-0650-1
  20. Shodeinde AL, Barton BE (2012). Potential use of STAT3 inhibitors in targeted prostate cancer therapy: future prospects. Onco Targets Ther, 5, 119-25.
  21. Skirnisdottir I, Seidal T (2013). Association of p21, p21 p27 and p21 p53 status to histological subtypes and prognosis in low-stage epithelial ovarian cancer. Cancer Genomics Proteomics, 10, 27-34.
  22. Son DS, Kabir SM, Dong YL, et al (2012). Inhibitory effect of tumor suppressor p53 on proinflammatory chemokine expression in ovarian cancer cells by reducing proteasomal degradation of I${\kappa}B$. PLoS One, 7, e51116. https://doi.org/10.1371/journal.pone.0051116
  23. Subramaniam A, Shanmugam MK, Perumal E, et al (2013). Potential role of signal transducer and activator of transcription (STAT) 3 signaling pathway in inflammation, survival, proliferation and invasion of hepatocellular carcinoma. Biochim Biophys Acta, 1835, 46-60.
  24. Swiatek-Machado K, Kaminska B (2013). STAT signaling in glioma cells. Adv Exp Med Biol, 986, 189-208. https://doi.org/10.1007/978-94-007-4719-7_10
  25. Thigpen JT, Vance RB, Khansur T (1993). Second-line chemotherapy for recurrent carcinoma of the ovary. Cancer, 71, 1559-64. https://doi.org/10.1002/cncr.2820710422
  26. Wang X, Crowe PJ, Goldstein D, et al (2012). STAT3 inhibition, a novel approach to enhancing targeted therapy in human cancers (Review). Int J Oncol, 41, 1181-91.
  27. Yang CL, Liu YY, Ma YG, et al (2012). Curcumin blocks small cell lung cancer cells migration, invasion, angiogenesis, cell cycle and neoplasia through Janus kinase-STAT3 signalling pathway. PLoS One,7, e37960. https://doi.org/10.1371/journal.pone.0037960

Cited by

  1. Radiation Induces Phosphorylation of STAT3 in a Dose- and Time-dependent Manner vol.15, pp.15, 2014, https://doi.org/10.7314/APJCP.2014.15.15.6161
  2. Preclinical Therapeutic Potential of a Nitrosylating Agent in the Treatment of Ovarian Cancer vol.9, pp.6, 2014, https://doi.org/10.1371/journal.pone.0097897
  3. Inhibition of Metastasis and Invasion of Ovarian Cancer Cells by Crude Polysaccharides from Rosa Roxburghii Tratt in Vitro vol.15, pp.23, 2015, https://doi.org/10.7314/APJCP.2014.15.23.10351
  4. Nitidine chloride inhibits ovarian cancer cell migration and invasion by suppressing MMP-2/9 production via the ERK signaling pathway vol.13, pp.4, 2016, https://doi.org/10.3892/mmr.2016.4929
  5. Nitidine chloride inhibits proliferation, induces apoptosis via the Akt pathway and exhibits a synergistic effect with doxorubicin in ovarian cancer cells vol.14, pp.3, 2016, https://doi.org/10.3892/mmr.2016.5577