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Article Open Access

Targeting CD146 in combination with vorinostat for the treatment of ovarian cancer cells

  • Authors:
    • Xiaoli Ma
    • Jiandong Wang
    • Jia Liu
    • Qingqing Mo
    • Xiyun Yan
    • Ding Ma
    • Hua Duan
  • View Affiliations / Copyright

    Affiliations: Gynecological Minimal Invasive Center, Beijing Obstetrics and Gynecology Hospital, Capital Medical University, Beijing 100006, P.R. China, Cancer Biology Research Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, P.R. China, Center of Molecular Biology, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, P.R. China
    Copyright: © Ma et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Pages: 1681-1687
    |
    Published online on: January 23, 2017
       https://doi.org/10.3892/ol.2017.5630
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Abstract

Drug resistance is the predominant cause of mortality in late‑stage patients with ovarian cancer. Histone deacetylase inhibitors (HDACis) have emerged as a novel type of second line drug with high specificity for tumor cells, including ovarian cancer cells. However, HDACis usually exhibit relatively low potencies when used as a single agent. The majority of current clinical trials are combination strategies. These strategies are more empirical than mechanism-based applications. Previously, it was reported that the adhesion molecule cluster of differentiation 146 (CD146) is significantly induced in HDACi‑treated tumor cells. The present study additionally confirmed that the induction of CD146 is a common phenomenon in vorinostat‑treated ovarian cancer cells. AA98, an anti‑CD146 monoclonal antibody (mAb), was used to target CD146 function. Synergistic antitumoral effects between AA98 and vorinostat were examined in vitro and in vivo. The potential effect of combined AA98 and vorinostat treatment on the protein kinase B (Akt) pathway was determined by western blotting. The present study found that targeting of CD146 substantially enhanced vorinostat‑induced killing via the suppression of activation of Akt pathways in ovarian cancer cells. AA98 in combination with vorinostat significantly inhibited cell proliferation and increased apoptosis. In vivo, AA98 synergized with vorinostat to inhibit tumor growth and prolong survival in ovarian cancer. These data suggest that an undesired induction of CD146 may serve as a protective response to offset the antitumor efficacy of vorinostat. By contrast, targeting CD146 in combination with vorinostat may be exploited as a novel strategy to more effectively kill ovarian cancer cells.
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1 

Suh DH, Lee KH, Kim K, Kang S and Kim JW: Major clinical research advances in gynecologic cancer in 2014. J Gynecol Oncol. 26:156–167. 2015. View Article : Google Scholar : PubMed/NCBI

2 

Jayson GC, Kohn EC, Kitchener HC and Ledermann JA: Ovarian cancer. Lancet. 384:1376–1388. 2014. View Article : Google Scholar : PubMed/NCBI

3 

Zahedi P, Yoganathan R, Piquette-Miller M and Allen C: Recent advances in drug delivery strategies for treatment of ovarian cancer. Expert Opin Drug Deliv. 9:567–583. 2012. View Article : Google Scholar : PubMed/NCBI

4 

Vecchione A, Belletti B, Lovat F, Volinia S, Chiappetta G, Giglio S, Sonego M, Cirombella R, Onesti EC, Pellegrini P, et al: A microRNA signature defines chemoresistance in ovarian cancer through modulation of angiogenesis. Proc Natl Acad Sci USA. 110:9845–9850. 2013. View Article : Google Scholar : PubMed/NCBI

5 

Zwergel C, Valente S, Jacob C and Mai A: Emerging approaches for histone deacetylase inhibitor drug discovery. Expert Opin Drug Discov. 10:599–613. 2015. View Article : Google Scholar : PubMed/NCBI

6 

Ma XL, Duan H, Liu J, Mo Q, Sun C, Ma D and Wang J: Effect of LIV1 on the sensitivity of ovarian cancer cells to trichostatin A. Oncol Rep. 33:893–898. 2015.PubMed/NCBI

7 

West AC and Johnstone RW: New and emerging HDAC inhibitors for cancer treatment. J Clin Invest. 124:30–39. 2014. View Article : Google Scholar : PubMed/NCBI

8 

Slingerland M, Guchelaar HJ and Gelderblom H: Histone deacetylase inhibitors: An overview of the clinical studies in solid tumors. Anticancer Drugs. 25:140–149. 2014. View Article : Google Scholar : PubMed/NCBI

9 

Højfeldt JW, Agger K and Helin K: Histone lysine demethylases as targets for anticancer therapy. Nat Rev Drug Discov. 12:917–930. 2013. View Article : Google Scholar : PubMed/NCBI

10 

Huang Z, Peng S, Knoff J, Lee SY, Yang B, Wu TC and Hung CF: Combination of proteasome and HDAC inhibitor enhances HPV16 E7-specific CD8+ T cell immune response and antitumor effects in a preclinical cervical cancer model. J Biomed Sci. 22:72015. View Article : Google Scholar : PubMed/NCBI

11 

Straus DJ, Hamlin PA, Matasar MJ, Lia Palomba M, Drullinsky PR, Zelenetz AD, Gerecitano JF, Noy A, Hamilton AM, Elstrom R, et al: Phase I/II trial of vorinostat with rituximab, cyclophosphamide, etoposide and prednisone as palliative treatment for elderly patients with relapsed or refractory diffuse large B-cell lymphoma not eligible for autologous stem cell transplantation. Br J Haematol. 168:663–670. 2015. View Article : Google Scholar : PubMed/NCBI

12 

Rasheed WK, Johnstone RW and Prince HM: Histone deacetylase inhibitors in cancer therapy. Expert Opin Investig Drugs. 16:659–678. 2007. View Article : Google Scholar : PubMed/NCBI

13 

Ma X, Liu J, Wu J, Yan X, Wu P, Liu Y, Li S, Tian Y, Cao Y, Chen G, et al: Synergistic killing effect between vorinostat and target of CD146 in malignant cells. Clin Cancer Res. 16:5165–5176. 2010. View Article : Google Scholar : PubMed/NCBI

14 

Wang Z and Yan X: CD146, a multi-functional molecule beyond adhesion. Cancer Lett. 330:150–162. 2013. View Article : Google Scholar : PubMed/NCBI

15 

Xie S, Luca M, Huang S, Gutman M, Reich R, Johnson JP and Bar-Eli M: Expression of MCAM/MUC18 by human melanoma cells leads to increased tumor growth and metastasis. Cancer Res. 57:2295–2303. 1997.PubMed/NCBI

16 

Wu GJ, Wu MW, Wang SW, Liu Z, Qu P, Peng Q, Yang H, Varma VA, Sun QC, Petros JA, et al: Isolation and characterization of the major form of human MUC18 cDNA gene and correlation of MUC18 over-expression in prostate cancer cell lines and tissues with malignant progression. Gene. 279:17–31. 2001. View Article : Google Scholar : PubMed/NCBI

17 

Zabouo G, Imbert AM, Jacquemier J, Finetti P, Moreau T, Esterni B, Birnbaum D, Bertucci F and Chabannon C: CD146 expression is associated with a poor prognosis in human breast tumors and with enhanced motility in breast cancer cell lines. Breast Cancer Res. 11:R12009. View Article : Google Scholar : PubMed/NCBI

18 

Leslie MC, Zhao YJ, Lachman LB, Hwu P, Wu GJ and Bar-Eli M: Immunization against MUC18/MCAM, a novel antigen that drives melanoma invasion and metastasis. Gene Ther. 14:316–323. 2007. View Article : Google Scholar : PubMed/NCBI

19 

Xing S, Luo Y, Liu Z, Bu P, Duan H, Liu D, Wang P, Yang J, Song L, Feng J, et al: Targeting endothelial CD146 attenuates colitis and prevents colitis-associated carcinogenesis. Am J Pathol. 184:1604–1616. 2014. View Article : Google Scholar : PubMed/NCBI

20 

Ma XL, Ma QF, Liu J, Tian Y, Wang B, Taylor KM, Wu P, Wang D, Xu G, Meng L, et al: Identification of LIV1, a putative zinc transporter gene responsible for HDACi-induced apoptosis, using a functional gene screen approach. Mol Cancer Ther. 8:3108–3116. 2009. View Article : Google Scholar : PubMed/NCBI

21 

Satyamoorthy K, Muyrers J, Meier F, Patel D and Herlyn M: Mel-CAM-specific genetic suppressor elements inhibit melanoma growth and invasion through loss of gap junctional communication. Oncogene. 20:4676–4684. 2001. View Article : Google Scholar : PubMed/NCBI

22 

Lei X, Guan CW, Song Y and Wang H: The multifaceted role of CD146/MCAM in the promotion of melanoma progression. Cancer Cell Int. 15:32015. View Article : Google Scholar : PubMed/NCBI

23 

Cooper AL, Greenberg VL, Lancaster PS, van Nagell JR Jr, Zimmer SG and Modesitt SC: In vitro and in vivo histone deacetylase inhibitor therapy with suberoylanilide hydroxamic acid (SAHA) and paclitaxel in ovarian cancer. Gynecol Oncol. 104:596–601. 2007. View Article : Google Scholar : PubMed/NCBI

24 

Zeng Q, Wu Z, Duan H, Jiang X, Tu T, Lu D, Luo Y, Wang P, Song L, Feng J, et al: Impaired tumor angiogenesis and VEGF-induced pathway in endothelial CD146 knockout mice. Protein Cell. 5:445–456. 2014. View Article : Google Scholar : PubMed/NCBI

25 

Lheureux S, Karakasis K, Kohn EC and Oza AM: Ovarian cancer treatment: The end of empiricism? Cancer. 121:3203–3211. 2015. View Article : Google Scholar : PubMed/NCBI

26 

Modugno F and Edwards RP: Ovarian cancer: Prevention, detection, and treatment of the disease and its recurrence. molecular mechanisms and personalized medicine meeting report. Int J Gynecol Cancer. 22:S45–S57. 2012. View Article : Google Scholar : PubMed/NCBI

27 

Bots M and Johnstone RW: Rational combinations using HDAC inhibitors. Clin Cancer Res. 15:3970–3977. 2009. View Article : Google Scholar : PubMed/NCBI

28 

Khabele D: The therapeutic potential of class I selective histone deacetylase inhibitors in ovarian cancer. Front Oncol. 20:1112014.

29 

Mohammad RM, Muqbil I, Lowe L, Yedjou C, Hsu HY, Lin LT, Siegelin MD, Fimognari C, Kumar NB, Dou QP, et al: Broad targeting of resistance to apoptosis in cancer. Semin Cancer Biol. 35:(Suppl). S78–S103. 2015. View Article : Google Scholar : PubMed/NCBI

30 

Ocana A, Vera-Badillo F, Al-Mubarak M, Templeton AJ, Corrales-Sanchez V, Diez-Gonzalez L, Cuenca-Lopez MD, Seruga B, Pandiella A and Amir E: Activation of the PI3K/mTOR/AKT pathway and survival in solid tumours: Systematic review and meta-analysis. PLoS One. 9:e952192014. View Article : Google Scholar : PubMed/NCBI

31 

Feng D, Cao Z, Li C, Zhang L, Zhou Y, Ma J, Liu R, Zhou H, Zhao W, Wei H and Ling B: Combination of valproic acid and ATRA restores RARβ2 expression and induces differentiation in cervical cancerthrough the PI3K/Akt pathway. Curr Mol Med. 12:342–354. 2012. View Article : Google Scholar : PubMed/NCBI

32 

Moschetta M, Reale A, Marasco C, Vacca A and Carratù MR: Therapeutic targeting of the mTOR-signalling pathway in cancer: Benefits and limitations. Br J Pharmacol. 171:3801–3813. 2014. View Article : Google Scholar : PubMed/NCBI

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Copy and paste a formatted citation
Spandidos Publications style
Ma X, Wang J, Liu J, Mo Q, Yan X, Ma D and Duan H: Targeting CD146 in combination with vorinostat for the treatment of ovarian cancer cells. Oncol Lett 13: 1681-1687, 2017.
APA
Ma, X., Wang, J., Liu, J., Mo, Q., Yan, X., Ma, D., & Duan, H. (2017). Targeting CD146 in combination with vorinostat for the treatment of ovarian cancer cells. Oncology Letters, 13, 1681-1687. https://doi.org/10.3892/ol.2017.5630
MLA
Ma, X., Wang, J., Liu, J., Mo, Q., Yan, X., Ma, D., Duan, H."Targeting CD146 in combination with vorinostat for the treatment of ovarian cancer cells". Oncology Letters 13.3 (2017): 1681-1687.
Chicago
Ma, X., Wang, J., Liu, J., Mo, Q., Yan, X., Ma, D., Duan, H."Targeting CD146 in combination with vorinostat for the treatment of ovarian cancer cells". Oncology Letters 13, no. 3 (2017): 1681-1687. https://doi.org/10.3892/ol.2017.5630
Copy and paste a formatted citation
x
Spandidos Publications style
Ma X, Wang J, Liu J, Mo Q, Yan X, Ma D and Duan H: Targeting CD146 in combination with vorinostat for the treatment of ovarian cancer cells. Oncol Lett 13: 1681-1687, 2017.
APA
Ma, X., Wang, J., Liu, J., Mo, Q., Yan, X., Ma, D., & Duan, H. (2017). Targeting CD146 in combination with vorinostat for the treatment of ovarian cancer cells. Oncology Letters, 13, 1681-1687. https://doi.org/10.3892/ol.2017.5630
MLA
Ma, X., Wang, J., Liu, J., Mo, Q., Yan, X., Ma, D., Duan, H."Targeting CD146 in combination with vorinostat for the treatment of ovarian cancer cells". Oncology Letters 13.3 (2017): 1681-1687.
Chicago
Ma, X., Wang, J., Liu, J., Mo, Q., Yan, X., Ma, D., Duan, H."Targeting CD146 in combination with vorinostat for the treatment of ovarian cancer cells". Oncology Letters 13, no. 3 (2017): 1681-1687. https://doi.org/10.3892/ol.2017.5630
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