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
March-2018 Volume 15 Issue 3

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
March-2018 Volume 15 Issue 3

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

Effects of PHA-665752 and vemurafenib combination treatment on in vitro and murine xenograft growth of human colorectal cancer cells with BRAFV600E mutations

  • Authors:
    • Jie Zhi
    • Zhongxin Li
    • Jian Lv
    • Bo Feng
    • Donghai Yang
    • Liang Xue
    • Zhaolong Zhao
    • Yanni Zhang
    • Jianhua Wu
    • Yingchao Jv
    • Yitao Jia
  • View Affiliations / Copyright

    Affiliations: Department of Oncology, Hebei General Hospital, Shijiazhuang, Hebei 050051, P.R. China, Second Department of Surgery, The Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei 050011, P.R. China, Experimental Animal Center, The Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei 050011, P.R. China
  • Pages: 3904-3910
    |
    Published online on: January 10, 2018
       https://doi.org/10.3892/ol.2018.7770
  • 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

It remains unknown whether blockade of B-Raf proto-oncogene, serine/threonine kinase (BRAF)V600E signaling and MET proto-oncogene, receptor tyrosine kinase (c‑Met) signaling is effective in suppressing the growth of human colorectal cancer (CRC) cells. The present study investigated the effects of the vemurafenib alone and in combination with c‑Met inhibitor PHA‑665752 on the growth of human CRC cells in vitro and in mouse xenografts. HT‑29 and RKO CRC cell lines with BRAFV600E mutations and mice bearing HT‑29 xenografts were treated with vemurafenib in the absence or presence of PHA‑665752. Cell viability and cycle phase were respectively examined by using the MTT and flow cytometry assay. Immunohistochemistry was conducted to detect the protein expression levels of hepatocyte growth factor (HGF), phosphorylated (p)-c‑Met, p‑AKT serine/threonine kinase (AKT) and p‑extracellular signal‑regulated kinase (p-ERK). The MTT assay demonstrated that the growth of RKO and HT‑29 cells was inhibited by PHA‑665752 in a time‑ and dose‑dependent manner (P<0.05), however no significant suppressive effects were observed with vemurafenib. Relative to the PHA‑665752 or vemurafenib stand‑alone treatment groups, the combination of PHA‑665752 and vemurafenib had a significant inhibitory effect on the proliferation of CRC cell lines (P<0.05). The mean tumor volume in mice treated with vemurafenib in combination with PHA‑665752 was significantly smaller compared with those treated with only vemurafenib or PHA‑665752 (P<0.05). Flow cytometry assay revealed that the G0/G1 phase frequency was significantly increased in the combination group compared with any other treatment groups (P<0.05). Immunohistochemistry demonstrated that vemurafenib in combination with PHA‑665752 effectively induced the expression of p‑c‑Met, p‑AKT and p‑ERK, however had no effect on HGF.
View Figures

Figure 1

Figure 2

Figure 3

Figure 4

Figure 5

View References

1 

Siegel RL, Miller KD and Jemal A: Cancer statistics, 2015. CA Cancer J Clin. 65:5–29. 2015. View Article : Google Scholar : PubMed/NCBI

2 

Lin PC, Yang YF, Tyan YC, Hsiao ES, Chu PC, Lee CT, Lee JC, Chen YM and Liao PC: Identification of Phosphorylated Cyclin-Dependent Kinase 1 Associated with Colorectal Cancer Survival Using Label-Free Quantitative Analyses. PLoS One. 11:e01588442016. View Article : Google Scholar : PubMed/NCBI

3 

Clarke CN and Kopetz ES: BRAF mutant colorectal cancer as a distinct subset of colorectal cancer: Clinical characteristics, clinical behavior, and response to targeted therapies. J Gastrointest Oncol. 6:660–667. 2015.PubMed/NCBI

4 

Chapman PB, Hauschild A, Robert C, Haanen JB, Ascierto P, Larkin J, Dummer R, Garbe C, Testori A, Maio M, et al: Improved survival with vemurafenib in melanoma with BRAF V600E mutation. N Engl J Med. 364:2507–2516. 2011. View Article : Google Scholar : PubMed/NCBI

5 

Cohen R, Cervera P, Svrcek M, Pellat A, Dreyer C, de Gramont A and André T: BRAF-mutated colorectal cancer: What is the optimal strategy for treatment. Curr Treat Options Oncol. 18:92017. View Article : Google Scholar : PubMed/NCBI

6 

Byeon HK, Na HJ, Yang YJ, Ko S, Yoon SO, Ku M, Yang J, Kim JW, Ban MJ, Kim JH, et al: Acquired resistance to BRAF inhibition induces epithelial-to-mesenchymal transition in BRAF (V600E) mutant thyroid cancer by c-Met-mediated AKT activation. Oncotarget. 8:596–609. 2017. View Article : Google Scholar : PubMed/NCBI

7 

Filitis DC, Rauh J and Mahalingam M: The HGF-cMET signaling pathway in conferring stromal-induced BRAF-inhibitor resistance in melanoma. Melanoma Res. 25:470–478. 2015. View Article : Google Scholar : PubMed/NCBI

8 

Gnad F, Doll S, Song K, Stokes MP, Moffat J, Liu B, Arnott D, Wallin J, Friedman LS, Hatzivassiliou G and Belvin M: Phosphoproteome analysis of the MAPK pathway reveals previously undetected feedback mechanisms. Proteomics. 16:1998–2004. 2016. View Article : Google Scholar : PubMed/NCBI

9 

Barresi V, Bonetti LR and Bettelli S: KRAS, NRAS, BRAF mutations and high counts of poorly differentiated clusters of neoplastic cells in colorectal cancer: Observational analysis of 175 cases. Pathology. 47:551–556. 2015. View Article : Google Scholar : PubMed/NCBI

10 

Gao J, Sun ZW, Li YY and Shen L: Mutations of KRAS and BRAF in Chinese patients with colorectal carcinoma: Analyses of 966 cases. Zhonghua Bing Li Xue Za Zhi. 41:579–583. 2012.(In Chinese). PubMed/NCBI

11 

Jang S, Hong M, Shin MK, Kim BC, Shin HS, Yu E, Hong SM, Kim J, Chun SM, Kim TI, et al: KRAS and PIK3CA mutations in colorectal adenocarcinomas correlate with aggressive histological features and behavior. Hum Pathol. 65:21–30. 2017. View Article : Google Scholar : PubMed/NCBI

12 

Chen CT, Kim H, Liska D, Gao S, Christensen JG and Weiser MR: MET activation mediates resistance to lapatinib inhibition of HER2-amplified gastric cancer cells. Mol Cancer Ther. 11:660–669. 2012. View Article : Google Scholar : PubMed/NCBI

13 

Joshi M, Rice SJ, Liu X, Miller B and Belani CP: Trametinib with or without vemurafenib in BRAF mutated non-small cell lung cancer. PLoS One. 10:e01182102015. View Article : Google Scholar : PubMed/NCBI

14 

Sikkandhar MG, Nedumaran AM, Ravichandar R, Singh S, Santhakumar I, Goh ZC, Mishra S, Archunan G, Gulyás B and Padmanabhan P: Theranostic probes for targeting tumor microenvironment: An overview. Int J Mol Sci. 18:pii: E10362017. View Article : Google Scholar

15 

Munn DH, Sharma MD, Johnson TS and Rodriguez P: IDO, PTEN-expressing Tregs and control of antigen-presentation in the murine tumor microenvironment. Cancer Immunol Immunother. 66:1049–1058. 2017. View Article : Google Scholar : PubMed/NCBI

16 

Casey SC, Amedei A, Aquilano K, Azmi AS, Benencia F, Bhakta D, Bilsland AE, Boosani CS, Chen S, Ciriolo MR, et al: Cancer prevention and therapy through the modulation of the tumor microenvironment. Semin Cancer Biol. 35 Suppl:S199–S223. 2015. View Article : Google Scholar : PubMed/NCBI

17 

Whitfield JR and Soucek L: Tumo r microenvironment: Becoming sick of Myc. Cell Mol Life Sci. 69:931–934. 2012. View Article : Google Scholar : PubMed/NCBI

18 

Rakhra K, Bachireddy P, Zabuawala T, Zeiser R, Xu L, Kopelman A, Fan AC, Yang Q, Braunstein L, Crosby E, et al: CD4(+) T cells contribute to the remodeling of the microenvironment required for sustained tumor regression upon oncogene inactivation. Cancer Cell. 18:485–498. 2010. View Article : Google Scholar : PubMed/NCBI

19 

Kenny PA, Lee GY and Bissell MJ: Targeting the tumor microenvironment. Front Biosci. 12:3468–3474. 2007. View Article : Google Scholar : PubMed/NCBI

20 

Kuo YH, Chiang EI, Chao CY, Rodriguez RL, Chou PY, Tsai SY, Pai MH and Tang FY: Dual inhibition of key proliferation signaling pathways in triple-negative breast cancer cells by a novel derivative of taiwanin A. Mol Cancer Ther. 16:480–493. 2017. View Article : Google Scholar : PubMed/NCBI

21 

Mann KM, Ying H, Juan J, Jenkins NA and Copeland NG: KRAS-related proteins in pancreatic cancer. Pharmacol Ther. 168:29–42. 2016. View Article : Google Scholar : PubMed/NCBI

22 

Bresin A, D'Abundo L, Narducci MG, Fiorenza MT, Croce CM, Negrini M and Russo G: TCL1 transgenic mouse model as a tool for the study of therapeutic targets and microenvironment in human B-cell chronic lymphocytic leukemia. Cell Death Dis. 7:e20712016. View Article : Google Scholar : PubMed/NCBI

23 

Krpina K, Babarović E, Španjol J, Đorđević G, Maurer T and Jonjić N: Correlation of tumor-associated macrophages and NK cells with bladder cancer size and T stage in patients with solitary low-grade urothelial carcinoma. Wien Klin Wochenschr. 128:248–252. 2016. View Article : Google Scholar : PubMed/NCBI

24 

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 tumors: Systematic review and meta-analysis. PLoS One. 9:e952192014. View Article : Google Scholar : PubMed/NCBI

25 

Baba Y, Tamura T, Satoh Y, Gotou M, Sawada H, Ebara S, Shibuya K, Soeda J and Nakamura K: Panitumumab interaction with TAS-102 leads to combinational anticancer effects via blocking of EGFR-mediated tumor response to trifluridine. Mol Oncol. 11:1065–1077. 2017. View Article : Google Scholar : PubMed/NCBI

26 

Liu L, Liao JZ, He XX and Li PY: The role of autophagy in hepatocellular carcinoma: Friend or foe. Oncotarget. 8:57707–57722. 2017.PubMed/NCBI

27 

Wang X, Shi W, Shi H, Lu S, Wang K, Sun C, He J, Jin W, Lv X, Zou H and Shu Y: TRIM11 overexpression promotes proliferation, migration and invasion of lung cancer cells. J Exp Clin Cancer Res. 35:1002016. View Article : Google Scholar : PubMed/NCBI

28 

He K, Chen D, Ruan H, Li X, Tong J, Xu X, Zhang L and Yu J: BRAFV600E-dependent Mcl-1 stabilization leads to everolimus resistance in colon cancer cells. Oncotarget. 7:47699–47710. 2016.PubMed/NCBI

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Zhi J, Li Z, Lv J, Feng B, Yang D, Xue L, Zhao Z, Zhang Y, Wu J, Jv Y, Jv Y, et al: Effects of PHA-665752 and vemurafenib combination treatment on in vitro and murine xenograft growth of human colorectal cancer cells with BRAFV600E mutations. Oncol Lett 15: 3904-3910, 2018.
APA
Zhi, J., Li, Z., Lv, J., Feng, B., Yang, D., Xue, L. ... Jia, Y. (2018). Effects of PHA-665752 and vemurafenib combination treatment on in vitro and murine xenograft growth of human colorectal cancer cells with BRAFV600E mutations. Oncology Letters, 15, 3904-3910. https://doi.org/10.3892/ol.2018.7770
MLA
Zhi, J., Li, Z., Lv, J., Feng, B., Yang, D., Xue, L., Zhao, Z., Zhang, Y., Wu, J., Jv, Y., Jia, Y."Effects of PHA-665752 and vemurafenib combination treatment on in vitro and murine xenograft growth of human colorectal cancer cells with BRAFV600E mutations". Oncology Letters 15.3 (2018): 3904-3910.
Chicago
Zhi, J., Li, Z., Lv, J., Feng, B., Yang, D., Xue, L., Zhao, Z., Zhang, Y., Wu, J., Jv, Y., Jia, Y."Effects of PHA-665752 and vemurafenib combination treatment on in vitro and murine xenograft growth of human colorectal cancer cells with BRAFV600E mutations". Oncology Letters 15, no. 3 (2018): 3904-3910. https://doi.org/10.3892/ol.2018.7770
Copy and paste a formatted citation
x
Spandidos Publications style
Zhi J, Li Z, Lv J, Feng B, Yang D, Xue L, Zhao Z, Zhang Y, Wu J, Jv Y, Jv Y, et al: Effects of PHA-665752 and vemurafenib combination treatment on in vitro and murine xenograft growth of human colorectal cancer cells with BRAFV600E mutations. Oncol Lett 15: 3904-3910, 2018.
APA
Zhi, J., Li, Z., Lv, J., Feng, B., Yang, D., Xue, L. ... Jia, Y. (2018). Effects of PHA-665752 and vemurafenib combination treatment on in vitro and murine xenograft growth of human colorectal cancer cells with BRAFV600E mutations. Oncology Letters, 15, 3904-3910. https://doi.org/10.3892/ol.2018.7770
MLA
Zhi, J., Li, Z., Lv, J., Feng, B., Yang, D., Xue, L., Zhao, Z., Zhang, Y., Wu, J., Jv, Y., Jia, Y."Effects of PHA-665752 and vemurafenib combination treatment on in vitro and murine xenograft growth of human colorectal cancer cells with BRAFV600E mutations". Oncology Letters 15.3 (2018): 3904-3910.
Chicago
Zhi, J., Li, Z., Lv, J., Feng, B., Yang, D., Xue, L., Zhao, Z., Zhang, Y., Wu, J., Jv, Y., Jia, Y."Effects of PHA-665752 and vemurafenib combination treatment on in vitro and murine xenograft growth of human colorectal cancer cells with BRAFV600E mutations". Oncology Letters 15, no. 3 (2018): 3904-3910. https://doi.org/10.3892/ol.2018.7770
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