Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress 2023 EHA Congress 2023 ASCO Annual Meeting
Clinical Collections
Advances in Alzheimer’s

At a glance: The ONWARDS insulin icodec trials

A round-up of the ONWARDS phase 3 clinical trials evaluating the novel weekly insulin icodec in people with diabetes.
ADVANCED SEARCH
Log in
Top
BMC Cancer
Published in: BMC Cancer 1/2016

Open Access 01-12-2016 | Research article

Combination of VP3 and CD147-knockdown enhance apoptosis and tumor growth delay index in colorectal tumor allograft

Authors: Ruzila Ismail, Zeenathul Nazariah Allaudin, Rasedee Abdullah, Mohd-Azmi Mohd Lila, Nik-Mohd-Afizan Nik Abd. Rahman, Sheikh-Omar Abdul Rahman

Published in: BMC Cancer | Issue 1/2016

Login to get access

Abstract

Background

Cancer therapies that kill cancer cells without affecting normal cells is the ultimate mode of treating cancers. The VP3, an avian virus-derived protein, can specifically initiate cell death through several signal transduction pathways leading to apoptosis. In cancer, chemoresistance and cell survivability implicate the cell surface protein, CD147.

Methods

In this study, transfection of VP3 and silencing of CD147 genes was achieved through the treatment of tumors with pVIVO1-GFP/VP3 (VP3), psiRNA-CD147/2 (shCD147/2), and their combination of CT26 colon cancer cell-induced in mice. The effectiveness of tumor-treatment was ascertained by electrophoresis, TUNEL assay, and flow cytometry analysis. While histopathological and biochemical analysis were used as toxic side effect identification.

Results

The tumor growth delay index (TGDI) after treatment with VP3, shCD147/2, and their combination treatments increased by 1.3-, 1.2-, 2.0- and 2.3-fold respectively, over untreated control. The VP3-shCD147/2 combination treatment was more efficacious then either VP3 or shCD147/2 alone in the retardation of mouse CT26 colorectal cell tumor allograft.

Conclusion

The antitumor effect of the combination treatment is the result of synergistic effects of VP3 and shCD147/2 on the tumor cells resulting in apoptosis. Thus, the study shows that combination of VP3 and shCD147/2 treatment can be developed into a potential approach for anticolorectal cancer treatment regimen.
Appendix
Available only for authorised users
Literature
1.
IARC. World Cancer Factsheet. Volume 2012. London: International Agency for Research on Cancer and Cancer Research © Copyright Cancer Research UK; 2014.
2.
IARC: GLOBOCAN 2012: Cancer Incidence and Mortality Worldwide. Available from: http://​globocan.​iarc.​fr, accessed on 27/08/14: International Agency for Research on Cancer © IARC 2014; 2014.
3.
Cunningham D, Atkin W, Lenz HJ, Lynch HT, Minsky B, Nordlinger B, Starling N. Colorectal cancer. Lancet. 2010;375:1030–47.CrossRefPubMed
4.
Kanekura T, Chen X, Kanzaki T. Basigin (CD147) is expressed on melanoma cells and induces tumor cell invasion by stimulating production of matrix metalloproteinases by fibroblasts. Int J Cancer. 2002;99:520–8.CrossRefPubMed
5.
Chen X, Lin J, Kanekura T, Su J, Lin W, Xie H, Wu Y, Li J, Chen M, Chang J. A small interfering CD147-targeting RNA inhibited the proliferation, invasiveness, and metastatic activity of malignant melanoma. Cancer Res. 2006;66:11323–30.CrossRefPubMed
6.
Taylor PM, Woodfield RJ, Hodgkin MN, Pettitt TR, Martin A, Kerr DJ, Wakelam MJO. Breast cancer cell-derived EMMPRIN stimulates fibroblast MMP2 release through a phospholipase A(2) and 5-lipoxygenase catalyzed pathway. Oncogene. 2002;21:5765–72.CrossRefPubMed
7.
Bordador LC, Li X, Toole B, Chen B, Regezi J, Zardi L, Hu Y, Ramos DM. Expression of emmprin by oral squamous cell carcinoma. Int J Cancer. 2000;85:347–52.CrossRefPubMed
8.
Stenzinger A, Wittschieber D, von Winterfeld M, Goeppert B, Kamphues C, Weichert W, Dietel M, Rabien A, Klauschen F. High extracellular matrix metalloproteinase inducer/CD147 expression is strongly and independently associated with poor prognosis in colorectal cancer. Hum Pathol. 2012;43:1471–81.CrossRefPubMed
9.
Su J, Chen X, Kanekura T. A CD147-targeting siRNA inhibits the proliferation, invasiveness, and VEGF production of human malignant melanoma cells by down-regulating glycolysis. Cancer Lett. 2009;273:140–7.CrossRefPubMed
10.
Ke X, Li L, Dong HL, Chen ZN. Acquisition of anoikis resistance through CD147 upregulation: A new mechanism underlying metastasis of hepatocellular carcinoma cells. Oncol Lett. 2012;3:1249–54.PubMedPubMedCentral
11.
Kuang YH, Chen X, Su J, Wu LS, Liao LQ, Li D, Chen ZS, Kanekura T. RNA interference targeting the CD147 induces apoptosis of multi-drug resistant cancer cells related to XIAP depletion. Cancer Lett. 2009;276:189–95.CrossRefPubMed
12.
Xiao L, Yan L, Zhongmei W, Chang L. Potent anti-tumor effects of a dual specific oncolytic adenovirus expressing apoptin in vitro and in vivo. Mol Cancer. 2010;9:1–12.CrossRef
13.
Visser AE, Backendorf C, Noteborn M. Viral protein apoptin as a molecular tool and therapeutic bullet: implications for cancer control. Future Virol. 2007;2:519–27.CrossRef
14.
Schoop RAL, Baatenburg de Jong RJ, Noteborn MHM. Apoptin induces apoptosis in an oral cancer mouse model. Cancer Biol Ther. 2008;7:1368–73.CrossRefPubMed
15.
Peng DJ, Sun J, Wang YZ, Tian J, Zhang YH, Noteborn MHM, Qu S. Inhibition of hepatocarcinoma by systemic delivery of Apoptin gene via the hepatic asialoglycoprotein receptor. Cancer Gene Ther. 2007;14:66–73.CrossRefPubMed
16.
Los M, Panigrahi S, Rashedi I, Mandal S, Stetefeld J, Essmann F, Schulze-Osthoff K. Apoptin, a tumor-selective killer. Biochim Biophys Acta. 2009;1793:1335–42.CrossRefPubMed
17.
Yuan L, Zhao H, Zhang L, Liu X. The efficacy of combination therapy using adeno-associated virus-mediated co-expression of apoptin and interleukin-24 on hepatocellular carcinoma. Tumor Biol. 2013;34:3027–34.CrossRef
18.
Lian H, Jin N, Li X, Mi Z, Zhang J, Sun L, Li X, Zheng H, Li P. Induction of an effective anti-tumor immune response and tumor regression by combined administration of IL-18 and Apoptin. Cancer Imunol Immunother. 2007;56:181–92.CrossRef
19.
Liu Q, Fu H, Xing R, Tie Y, Zhu J, Sun Z, Zheng X. Survivin knockdown combined with apoptin overexpression inhibits cell growth significantly. Cancer Biol Ther. 2008;7:1053–60.CrossRefPubMed
20.
Ismail R, Allaudin ZN, Nik Abd Rahman NMA, Abd Rahman SO, Mustafa N, Mohd Lila MA. Tissue distribution of intramuscularly and intratumouraly administered DNA plasmid harbouring apoptotic gene in mice. Afr J Pharmac Pharmacol. 2010;4:775–82.
21.
Teicher BA. Preclinical tumor response end points. In: Teicher BA, editor. Tumor Models in Cancer Research. Totowa: Humana Press; 2011. p. 571–605.CrossRef
22.
Sancéau J, Poupon MF, Delattre O, Sastre-Garau X, Wietzerbin J. Strong inhibition of Ewing tumor xenograft growth by combination of human interferon-alpha or interferon-beta with ifosfamide. Oncogene. 2002;21:7700–9.CrossRefPubMed
23.
Griswold DP, Corbett TH. A colon tumor model for anticancer agent evaluation. Cancer. 1975;36:2441–4.CrossRefPubMed
24.
Castle JC, Loewer M, Boegel S, de Graaf J, Bender C, Tadmor AD, Boisguerin V, Bukur T, Sorn P, Paret C, Diken M, Kreiter S, Türeci Ö, Sahin U. Immunomic, genomic and transcriptomic characterization of CT26 colorectal carcinoma. BMC Genomics. 2014;15:190.CrossRefPubMedPubMedCentral
25.
Pietersen AM, Van Der Eb MM, Rademaker HJ, Van Den Wollenberg DJM, Rabelink MJWE, Kuppen PJK, Van Dierendonck JH, Van Ormondt H, Masman D, Van De Velde CJH, Van Der Eb AJ, Hoeben RC, Noteborn MHM. Specific tumor-cell killing with adenovirus vectors containing the apoptin gene. Gene Ther. 1999;6:882–92.CrossRefPubMed
26.
Nik Abd Rahman NMA, Allaudin ZN, Mohd MN, Ismail R, Mustafa N, Mohd Lila MA. Apoptosis and tumour cell death in response to pro-apoptotic gene. Pertanika J Trop Agric Sci. 2011;34:163–6.
27.
Van der Eb MM, Pietersen AM, Speetjens FM, Kuppen PJK, Van De Velde CJH, Noteborn MHM, Hoeben RC. Gene therapy with apoptin induces regression of xenografted human hepatomas. Cancer Gene Ther. 2002;9:53–61.CrossRefPubMed
28.
Lee AS. The glucose-regulated proteins: stress induction and clinical applications. Trends Biochem Sci. 2001;26:504–10.CrossRefPubMed
29.
Chen X, Zhang D, Dennert G, Hung G, Lee AS. Eradication of murine mammary adenocarcinoma through HSVtk expression directed by the glucose-starvation inducible grp78 promoter. Breast Cancer Res Treat. 2000;59:81–90.CrossRefPubMed
30.
Gazit G, Hung G, Chen X, Anderson WF, Lee AS. Use of the glucose starvation-inducible glucose-regulated protein 78 promoter in suicide gene therapy of murine fibrosarcoma. Cancer Res. 1999;59:3100–6.PubMed
31.
Abraham D, Zins K, Sioud M, Lucas T, Aharinejad S. Host CD147 blockade by small interfering RNAs suppresses growth of human colon cancer xenografts. Front Biosci. 2008;13:5571–9.CrossRefPubMed
32.
Wang B, Xu YF, He BS, Pan YQ, Zhang LR, Zhu C, Qu LL, Wang SK. RNAi-mediated silencing of CD147 inhibits tumor cell proliferation, invasion and increases chemosensitivity to cisplatin in SGC7901 cells in vitro. J Exp Clin Cancer Res. 2010;29:1–8.CrossRef
33.
Gorman AM, Szegezdi E, Quigney DJ, Samali A. Hsp27 inhibits 6-hydroxydopamine-induced cytochrome c release and apoptosis in PC12 cells. Biochem Biophys Res Commun. 2005;327:801–10.CrossRefPubMed
34.
Ejima K, Koji T, Tsuruta D, Nanri H, Kashimura M, Ikeda M. Induction of Apoptosis in Placentas of Pregnant Mice Exposed to Lipopolysaccharides: Possible Involvement of Fas/Fas Ligand System. Biol Reprod. 2000;62:178–85.CrossRefPubMed
35.
Chang CJ, Shih WL, Yu FL, Liao MH, Liu HJ. Apoptosis induced by bovine ephemeral fever virus. J Virol Methods. 2004;122:165–70.CrossRefPubMed
36.
Paoli P, Giannoni E, Chiarugi P. Anoikis molecular pathways and its role in cancer progression. Biochim Biophys Acta. 1833;2013:3481–98.
37.
38.
Metadata
Title
Combination of VP3 and CD147-knockdown enhance apoptosis and tumor growth delay index in colorectal tumor allograft
Authors
Ruzila Ismail
Zeenathul Nazariah Allaudin
Rasedee Abdullah
Mohd-Azmi Mohd Lila
Nik-Mohd-Afizan Nik Abd. Rahman
Sheikh-Omar Abdul Rahman
Publication date
01-12-2016
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2016
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/s12885-016-2530-8

Other articles of this Issue 1/2016

BMC Cancer 1/2016 Go to the issue

Research article

Osteopontin regulates proliferation, apoptosis, and migration of murine claudin-low mammary tumor cells

Research article

The pretreatment Controlling Nutritional Status (CONUT) score is an independent prognostic factor in patients with resectable thoracic esophageal squamous cell carcinoma: results from a retrospective study

Research article

The combination of serum insulin, osteopontin, and hepatocyte growth factor predicts time to castration-resistant progression in androgen dependent metastatic prostate cancer- an exploratory study

Research article

Activins and their related proteins in colon carcinogenesis: insights from early and advanced azoxymethane rat models of colon cancer

Research article

Biochemical markers of bone turnover in patients with spinal metastases after resistance training under radiotherapy – a randomized trial

Case report

A rare case of extremely high counts of circulating tumor cells detected in a patient with an oral squamous cell carcinoma
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Watch now

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine
Image Credits