Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Oncology Letters
      • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Biomedical Reports
      • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • Information for Authors
    • Information for Reviewers
    • Information for Librarians
    • Information for Advertisers
    • Conferences
  • Language Editing
Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • For Authors
    • For Reviewers
    • For Librarians
    • For Advertisers
    • Conferences
  • Language Editing
Login Register Submit
  • This site uses cookies
  • You can change your cookie settings at any time by following the instructions in our Cookie Policy. To find out more, you may read our Privacy Policy.

    I agree
Search articles by DOI, keyword, author or affiliation
Search
Advanced Search
presentation
Oncology Letters
Join Editorial Board Propose a Special Issue
Print ISSN: 1792-1074 Online ISSN: 1792-1082
Journal Cover
May-2016 Volume 11 Issue 5

Full Size Image

Sign up for eToc alerts
Recommend to Library

Journals

International Journal of Molecular Medicine

International Journal of Molecular Medicine

International Journal of Molecular Medicine is an international journal devoted to molecular mechanisms of human disease.

International Journal of Oncology

International Journal of Oncology

International Journal of Oncology is an international journal devoted to oncology research and cancer treatment.

Molecular Medicine Reports

Molecular Medicine Reports

Covers molecular medicine topics such as pharmacology, pathology, genetics, neuroscience, infectious diseases, molecular cardiology, and molecular surgery.

Oncology Reports

Oncology Reports

Oncology Reports is an international journal devoted to fundamental and applied research in Oncology.

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine is an international journal devoted to laboratory and clinical medicine.

Oncology Letters

Oncology Letters

Oncology Letters is an international journal devoted to Experimental and Clinical Oncology.

Biomedical Reports

Biomedical Reports

Explores a wide range of biological and medical fields, including pharmacology, genetics, microbiology, neuroscience, and molecular cardiology.

Molecular and Clinical Oncology

Molecular and Clinical Oncology

International journal addressing all aspects of oncology research, from tumorigenesis and oncogenes to chemotherapy and metastasis.

World Academy of Sciences Journal

World Academy of Sciences Journal

Multidisciplinary open-access journal spanning biochemistry, genetics, neuroscience, environmental health, and synthetic biology.

International Journal of Functional Nutrition

International Journal of Functional Nutrition

Open-access journal combining biochemistry, pharmacology, immunology, and genetics to advance health through functional nutrition.

International Journal of Epigenetics

International Journal of Epigenetics

Publishes open-access research on using epigenetics to advance understanding and treatment of human disease.

Medicine International

Medicine International

An International Open Access Journal Devoted to General Medicine.

Journal Cover
May-2016 Volume 11 Issue 5

Full Size Image

Sign up for eToc alerts
Recommend to Library

  • Article
  • Citations
    • Cite This Article
    • Download Citation
    • Create Citation Alert
    • Remove Citation Alert
    • Cited By
  • Similar Articles
    • Related Articles (in Spandidos Publications)
    • Similar Articles (Google Scholar)
    • Similar Articles (PubMed)
  • Download PDF
  • Download XML
  • View XML
Article

Synergistic antitumor activity of gemcitabine combined with triptolide in pancreatic cancer cells

  • Authors:
    • Zhixin Qiao
    • Min He
    • Mu He
    • Weijing Li
    • Xuanlin Wang
    • Yanbing Wang
    • Qiyuan Kuai
    • Changlan Li
    • Suping Ren
    • Qun Yu
  • View Affiliations / Copyright

    Affiliations: Department of Blood Products and Substitutes, Beijing Institute of Transfusion Medicine, Beijing 100850, P.R. China
  • Pages: 3527-3533
    |
    Published online on: March 29, 2016
       https://doi.org/10.3892/ol.2016.4379
  • Expand metrics +
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )
Cited By (CrossRef): 0 citations Loading Articles...

This article is mentioned in:



Abstract

Pancreatic cancer is a fatal human malignancy associated with an exceptionally poor prognosis. Novel therapeutic strategies are urgently required to treat this disease. In addition to immunosuppressive activity, triptolide possesses strong antitumor activity and synergistically enhances the antitumor activities of conventional chemotherapeutic drugs in preclinical models of pancreatic cancer. The present study investigated the antitumor effects of triptolide in pancreatic cancer cells, either in combination with gemcitabine, or alone. The pancreatic cancer BxPC‑3 and PANC‑1 cell lines were treated with triptolide, which resulted in time‑ and dose‑dependent growth arrest. When incorporated into a sequential schedule, triptolide synergistically increased gemcitabine‑induced cell growth inhibition and apoptosis, in addition to the cooperative regulation of B‑cell lymphoma 2 family proteins and loss of mitochondrial membrane potential. Furthermore, triptolide enhanced gemcitabine‑induced S phase arrest and DNA double‑strand breaks, possibly through checkpoint kinase 1 suppression. The results of the present study suggest that triptolide has therapeutic potential for the treatment of pancreatic cancer, particularly when administered in combination with gemcitabine.
View Figures

Figure 1

Figure 2

Figure 3

Figure 4

View References

1 

Shaib YH, Davila JA and El-Serag B: The epidemiology of pancreatic cancer in the United States: Changes below the surface. Aliment Pharmacol Ther. 24:87–94. 2006. View Article : Google Scholar : PubMed/NCBI

2 

Rosenberg L: Pancreatic cancer: A review of emerging therapies. Drugs. 59:1071–1089. 2000. View Article : Google Scholar : PubMed/NCBI

3 

Siegel R, Ma J, Zou Z and Jemal A: Cancer statistics, 2014. CA Cancer J Clin. 64:9–29. 2014. View Article : Google Scholar : PubMed/NCBI

4 

Freelove R and Walling AD: Pancreatic cancer: Diagnosis and management. Am Fam Physician. 73:485–492. 2006.PubMed/NCBI

5 

Bilimoria KY, Bentrem DJ, Ko CY, Stewart AK, Winchester DP and Talamonti MS: National failure to operate on early stage pancreatic cancer. Ann Surg. 246:173–180. 2007. View Article : Google Scholar : PubMed/NCBI

6 

Zuckerman DS and Ryan DP: Adjuvant therapy for pancreatic cancer: A review. Cancer. 112:243–249. 2008. View Article : Google Scholar : PubMed/NCBI

7 

Rothenberg ML, Moore MJ, Cripps MC, Andersen JS, Portenoy RK, Burris HA III, Green MR, Tarassoff PG, Brown TD, Casper ES, et al: A phase II trial of gemcitabine in patients with 5-FU-refractory pancreas cancer. Ann Oncol. 7:347–353. 1996. View Article : Google Scholar : PubMed/NCBI

8 

Burris HA III, Moore MJ, Andersen J, et al: Improvements in survival and clinical benefit with gemcitabine as first-line therapy for patients with advanced pancreas cancer: A randomized trial. J Clin Oncol. 15:2403–2413. 1997.PubMed/NCBI

9 

Mini E, Nobili S, Caciagli B, Landini I and Mazzei T: Cellular pharmacology of gemcitabine. Ann Oncol. 17(Suppl 5): v7–v12. 2006. View Article : Google Scholar : PubMed/NCBI

10 

Schultz RM, Merriman RL, Toth JE, Zimmermann JE, Hertel LW, Andis SL, Dudley DE, Rutherford PG, Tanzer LR and Grindey GB: Evaluation of new anticancer agents against the MIA PaCa-2 and PANC-1 human pancreatic carcinoma xenografts. Oncol Res. 5:223–228. 1993.PubMed/NCBI

11 

Nakano Y, Tanno S, Koizumi K, Nishikawa T, Nakamura K, Minoguchi M, Izawa T, Mizukami Y, Okumura T and Kohgo Y: Gemcitabine chemoresistance and molecular markers associated with gemcitabine transport and metabolism in human pancreatic cancer cells. Br J Cancer. 96:457–463. 2007. View Article : Google Scholar : PubMed/NCBI

12 

Xu B, Guo X, Mathew S, Armesilla AL, Cassidy J, Darling JL and Wang W: Triptolide simultaneously induces reactive oxygen species, inhibits NF-kappaB activity and sensitizes 5-fluorouracil in colorectal cancer cell lines. Cancer Lett. 291:200–208. 2010. View Article : Google Scholar : PubMed/NCBI

13 

Qiu D, Zhao G, Aoki Y, Shi L, Uyei A, Nazarian S, Ng JC and Kao PN: Immunosuppressant PG490 (triptolide) inhibits T-cell interleukin-2 expression at the level of purine-box/nuclear factor of activated T-cells and NF-kappaB transcriptional activation. J Biol Chem. 274:13443–13450. 1999. View Article : Google Scholar : PubMed/NCBI

14 

Liu Q: Triptolide and its expanding multiple pharmacological functions. Int Immunopharmacol. 11:377–383. 2011. View Article : Google Scholar : PubMed/NCBI

15 

Brinker AM, Ma J, Lipsky PE and Raskin I: Medicinal chemistry and pharmacology of genus Tripterygium (Celastraceae). Phytochemistry. 68:732–766. 2007. View Article : Google Scholar : PubMed/NCBI

16 

Huang W, He T, Chai C, Yang Y, Zheng Y, Zhou P, Qiao X, Zhang B, Liu Z, Wang J, et al: Triptolide inhibits the proliferation of prostate cancer cells and down-regulates SUMO-specific protease 1 expression. PLoS One. 7:e376932012. View Article : Google Scholar : PubMed/NCBI

17 

Phillips PA, Dudeja V, McCarroll JA, Borja-Cacho D, Dawra RK, Grizzle WE, Vickers SM and Saluja AK: Triptolide induces pancreatic cancer cell death via inhibition of heat shock protein 70. Cancer Res. 67:9407–9416. 2007. View Article : Google Scholar : PubMed/NCBI

18 

Shamon LA, Pezzuto JM, Graves JM, Mehta RR, Wangcharoentrakul S, Sangsuwan R, Chaichana S, Tuchinda P, Cleason P and Reutrakul V: Evaluation of the mutagenic, cytotoxic and antitumor potential of triptolide, a highly oxygenated diterpene isolated from Tripterygium wilfordii. Cancer Lett. 112:113–117. 1997. View Article : Google Scholar : PubMed/NCBI

19 

Li CJ, Chu CY, Huang LH, Wang MH, Sheu LF, Yeh JI and Hsu HY: Synergistic anticancer activity of triptolide combined with cisplatin enhances apoptosis in gastric cancer in vitro and in vivo. Cancer Lett. 319:203–213. 2012. View Article : Google Scholar : PubMed/NCBI

20 

Chen YW, Lin GJ, Chuang YP, Chia WT, Hueng DY, Lin CK, Nieh S and Sytwu HK: Triptolide circumvents drug-resistant effect and enhances 5-fluorouracil antitumor effect on KB cells. Anticancer Drugs. 21:502–513. 2010. View Article : Google Scholar : PubMed/NCBI

21 

Zhu W, Li J, Wu S, Li S, Le L, Su X, Qiu P, Hu H and Yan G: Triptolide cooperates with Cisplatin to induce apoptosis in gemcitabine-resistant pancreatic cancer. Pancreas. 41:1029–1038. 2012. View Article : Google Scholar : PubMed/NCBI

22 

Liu Y and Cui YF: Synergism of cytotoxicity effects of triptolide and artesunate combination treatment in pancreatic cancer cell lines. Asian Pac J Cancer Prev. 14:5243–5248. 2013. View Article : Google Scholar : PubMed/NCBI

23 

Yang SW, Wang W, Xie XY, Zhu WP and Li FQ: In vitro synergistic cytotoxic effect of triptolide combined with hydroxycamptothecin on pancreatic cancer cells. Am J Chin Med. 39:121–134. 2011. View Article : Google Scholar : PubMed/NCBI

24 

Kiviharju TM, Lecane PS, Sellers RG and Peehl DM: Antiproliferative and proapoptotic activities of triptolide (PG490), a natural product entering clinical trials, on primary cultures of human prostatic epithelial cells. Clin Cancer Res. 8:2666–2674. 2002.PubMed/NCBI

25 

Qiao Z, Ren S, Li W, Wang X, He M, Guo Y, Sun L, He Y, Ge Y and Yu Q: Chidamide, a novel histone deacetylase inhibitor, synergistically enhances gemcitabine cytotoxicity in pancreatic cancer cells. Biochem Biophys Res Commun. 434:95–101. 2013. View Article : Google Scholar : PubMed/NCBI

26 

Donadelli M, Costanzo C, Beghelli S, Scupoli MT, Dandrea M, Bonora A, Piacentini P, Budillon A, Caraglia M, Scarpa A and Palmieri M: Synergistic inhibition of pancreatic adenocarcinoma cell growth by trichostatin A and gemcitabine. Biochim Biophys Acta. 1773:1095–1106. 2007. View Article : Google Scholar : PubMed/NCBI

27 

Xie C, Edwards H, Xu X, Zhou H, Buck SA, Stout ML, Yu Q, Rubnitz JE, Matherly LH, Taub JW and Ge Y: Mechanisms of synergistic antileukemic interactions between valproic acid and cytarabine in pediatric acute myeloid leukemia. Clin Cancer Res. 16:5499–5510. 2010. View Article : Google Scholar : PubMed/NCBI

28 

Xiang M, Qian ZY, Zhou CH, Liu J and Li WN: Crocetin inhibits leukocyte adherence to vascular endothelial cells induced by AGEs. J Ethnopharmacol. 107:25–31. 2006. View Article : Google Scholar : PubMed/NCBI

29 

Kinnally KW and Antonsson B: A tale of two mitochondrial channels, MAC and PTP, in apoptosis. Apoptosis. 12:857–868. 2007. View Article : Google Scholar : PubMed/NCBI

30 

Dai Y and Grant S: New insights into checkpoint kinase 1 in the DNA damage response signaling network. Clin Cancer Res. 16:376–383. 2010. View Article : Google Scholar : PubMed/NCBI

31 

Kupchan SM, Court WA, Dailey RG Jr..Gilmore CJ and Bryan RF: Triptolide and tripdiolide, novel antileukemic diterpenoid triepoxides from Tripterygium wilfordii. J Am Chem Soc. 94:7194–7195. 1972. View Article : Google Scholar : PubMed/NCBI

32 

Hu YP, Tan ZJ, Wu XS, Liu TY, Jiang L, Bao RF, Shu YJ, Li ML, Weng H, Ding Q, Tao F and Liu YB: Triptolide induces s phase arrest and apoptosis in gallbladder cancer cells. Molecules. 2014.19(2): 2612–2628. View Article : Google Scholar : PubMed/NCBI

33 

Ho JN, Byun SS, Lee S, Oh JJ, Hong SK, Lee SE and Yeon JS: Synergistic antitumor effect of triptolide and cisplatin in cisplatin resistant human bladder cancer cells. The Journal of urology. 2015.193(3): 1016–1022, 14. View Article : Google Scholar : PubMed/NCBI

34 

Chueh FS, Chen YL, Hsu SC, Yang JS, Hsueh SC, Ji BC, Lu HF and Chung JG: Triptolide induced DNA damage in A375.S2 human malignant melanoma cells is mediated via reduction of DNA repair genes. Oncol Rep. 29:613–618. 2013.PubMed/NCBI

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Qiao Z, He M, He M, Li W, Wang X, Wang Y, Kuai Q, Li C, Ren S, Yu Q, Yu Q, et al: Synergistic antitumor activity of gemcitabine combined with triptolide in pancreatic cancer cells. Oncol Lett 11: 3527-3533, 2016.
APA
Qiao, Z., He, M., He, M., Li, W., Wang, X., Wang, Y. ... Yu, Q. (2016). Synergistic antitumor activity of gemcitabine combined with triptolide in pancreatic cancer cells. Oncology Letters, 11, 3527-3533. https://doi.org/10.3892/ol.2016.4379
MLA
Qiao, Z., He, M., He, M., Li, W., Wang, X., Wang, Y., Kuai, Q., Li, C., Ren, S., Yu, Q."Synergistic antitumor activity of gemcitabine combined with triptolide in pancreatic cancer cells". Oncology Letters 11.5 (2016): 3527-3533.
Chicago
Qiao, Z., He, M., He, M., Li, W., Wang, X., Wang, Y., Kuai, Q., Li, C., Ren, S., Yu, Q."Synergistic antitumor activity of gemcitabine combined with triptolide in pancreatic cancer cells". Oncology Letters 11, no. 5 (2016): 3527-3533. https://doi.org/10.3892/ol.2016.4379
Copy and paste a formatted citation
x
Spandidos Publications style
Qiao Z, He M, He M, Li W, Wang X, Wang Y, Kuai Q, Li C, Ren S, Yu Q, Yu Q, et al: Synergistic antitumor activity of gemcitabine combined with triptolide in pancreatic cancer cells. Oncol Lett 11: 3527-3533, 2016.
APA
Qiao, Z., He, M., He, M., Li, W., Wang, X., Wang, Y. ... Yu, Q. (2016). Synergistic antitumor activity of gemcitabine combined with triptolide in pancreatic cancer cells. Oncology Letters, 11, 3527-3533. https://doi.org/10.3892/ol.2016.4379
MLA
Qiao, Z., He, M., He, M., Li, W., Wang, X., Wang, Y., Kuai, Q., Li, C., Ren, S., Yu, Q."Synergistic antitumor activity of gemcitabine combined with triptolide in pancreatic cancer cells". Oncology Letters 11.5 (2016): 3527-3533.
Chicago
Qiao, Z., He, M., He, M., Li, W., Wang, X., Wang, Y., Kuai, Q., Li, C., Ren, S., Yu, Q."Synergistic antitumor activity of gemcitabine combined with triptolide in pancreatic cancer cells". Oncology Letters 11, no. 5 (2016): 3527-3533. https://doi.org/10.3892/ol.2016.4379
Follow us
  • Twitter
  • LinkedIn
  • Facebook
About
  • Spandidos Publications
  • Careers
  • Cookie Policy
  • Privacy Policy
How can we help?
  • Help
  • Live Chat
  • Contact
  • Email to our Support Team