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
Clinical Collections
Advances in Alzheimer’s

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.
ADVANCED SEARCH
Log in
Top
Journal of Cancer Research and Clinical Oncology
Published in: Journal of Cancer Research and Clinical Oncology 3/2015

01-03-2015 | Original Article – Cancer Research

Synergistic suppression effect on tumor growth of hepatocellular carcinoma by combining oncolytic adenovirus carrying XAF1 with cisplatin

Authors: Buyun Ma, Yanchun Wang, Xiumei Zhou, Panpan Huang, Rong Zhang, Tao Liu, Caixia Cui, Xinyuan Liu, Yigang Wang

Published in: Journal of Cancer Research and Clinical Oncology | Issue 3/2015

Login to get access

Abstract

Purpose

The potent anticancer efficacy of oncolytic viruses has been verified in Clinic in recent years. Cisplatin (DDP) is one of most common chemotherapeutic drugs, but is accompanied by side effects and drug resistance. Our previous studies have shown the strategy of cancer -targeting gene-viro-therapy (CTGVT) mediated by the oncolytic virus ZD55 containing the XAF1 cDNA (ZD55-XAF1), which exhibited potent antitumor effects in various tumor cells and no apparent toxicities on normal cells. In the study, the CTGVT strategy is broadened by combining DDP with ZD55-XAF1 for growth inhibition of hepatocellular carcinoma (HCC) cells.

Methods

The transgenic expression was evaluated by both in vitro and in vivo experiments, and the enhanced inhibitory effect of ZD55-XAF1 combined with cisplatin was assessed in HCC cells. The cytotoxicity on normal liver cells was evaluated by MTT assay and apoptotic cell staining. Activation of caspase-9 and PARP for apoptosis was further detected by Western blot analysis. The in vivo antitumor efficacy of combination treatment with cisplatin and ZD55-XAF1 was estimated in an HCC xenograft mouse model.

Results

We found that the combination of ZD55-XAF1 and cisplatin showed enhanced inhibitory effects on the proliferation of HCC cells in vitro and tumor growth in mice. Furthermore, the combined treatment of ZD55-XAF1 and DDP decreases the chemotherapy dose needed to achieve the same inhibitory effect without overlapping toxicities on normal liver cells and induces tumor cell apoptosis via the activation of caspase-9/PARP pathway.

Conclusion

Thus, these data suggest that the chemo-gene-viro-therapeutic strategy by combining ZD55-XAF1 and DDP reveals a novel therapeutic strategy for hepatocellular carcinoma.
Literature
Bisht S, Bhakta G, Mitra S, Maitra A (2005) pDNA loaded calcium phosphate nanoparticles: highly efficient non-viral vector for gene delivery. Int J Pharm 288:157–168CrossRefPubMed
Breitbach CJ, Burke J, Jonker D, Stephenson J, Haas AR, Chow LQ, Nieva J, Hwang T-H, Moon A, Patt R (2011) Intravenous delivery of a multi-mechanistic cancer-targeted oncolytic poxvirus in humans. Nature 477:99–102CrossRefPubMed
Dan HC, Sun M, Kaneko S, Feldman RI, Nicosia SV, Wang H-G, Tsang BK, Cheng JQ (2004) Akt phosphorylation and stabilization of X-linked inhibitor of apoptosis protein (XIAP). J Biol Chem 279:5405–5412CrossRefPubMed
Fong WG, Liston P, Rajcan-Separovic E, St Jean M, Craig C, Korneluk RG (2000) Expression and genetic analysis of XIAP-associated factor 1 (XAF1) in cancer cell lines. Genomics 70:113–122CrossRefPubMed
Ganly I, Kirn D, Eckhardt SG, Rodriguez GI, Soutar DS, Otto R, Robertson AG, Park O, Gulley ML, Heise C (2000) A phase I study of Onyx-015, an E1B attenuated adenovirus, administered intratumorally to patients with recurrent head and neck cancer. Clin Cancer Res 6:798–806PubMed
He G, Lei W, Wang S, Xiao R, Guo K, Xia Y, Zhou X, Zhang K, Liu X, Wang Y (2012) Overexpression of tumor suppressor TSLC1 by a survivin-regulated oncolytic adenovirus significantly inhibits hepatocellular carcinoma growth. J Cancer Res Clin Oncol 138:657–670CrossRefPubMed
Heise C, Sampson-Johannes A, Williams A, Mccormick F, Von Hoff DD, Kirn DH (1997) ONYX-015, an E1B gene-attenuated adenovirus, causes tumor-specific cytolysis and antitumoral efficacy that can be augmented by standard chemotherapeutic agents. Nat Med 3:639–645CrossRefPubMed
Khuri FR, Nemunaitis J, Ganly I, Arseneau J, Tannock IF, Romel L, Gore M, Ironside J, MacDougall R, Heise C (2000) A controlled trial of intratumoral ONYX-015, a selectively-replicating adenovirus, in combination with cisplatin and 5-fluorouracil in patients with recurrent head and neck cancer. Nat Med 6:879–885CrossRefPubMed
Kirn D (2001) Oncolytic virotherapy for cancer with the adenovirus dl1520 (Onyx-015): results of phase I and II trials. Expert Opin Biol Ther 1:525–538CrossRefPubMed
Kirn D, Hermiston T, McCormick F (1998) ONYX-015: clinical data are encouraging. Nat Med 4:1341–1342CrossRefPubMed
Leaman DW, Chawla-Sarkar M, Vyas K, Reheman M, Tamai K, Toji S, Borden EC (2002) Identification of X-linked inhibitor of apoptosis-associated factor-1 as an interferon-stimulated gene that augments TRAIL Apo2L-induced apoptosis. J Biol Chem 277:28504–28511CrossRefPubMed
Liston P, Fong WG, Kelly NL, Toji S, Miyazaki T, Conte D, Tamai K, Craig CG, McBurney MW, Korneluk RG (2001) Identification of XAF1 as an antagonist of XIAP anti-Caspase activity. Nat Cell Biol 3:128–133CrossRefPubMed
Ma TL, Ni PH, Zhong J, Tan JH, Qiao MM, Jiang SH (2005) Low expression of XIAP-associated factor 1 in human colorectal cancers. Chin J Dig Dis 6:10–14CrossRefPubMed
Momparler RL, Karon M, Siegel SE, Avila F (1976) Effect of adriamycin on DNA, RNA, and protein synthesis in cell-free systems and intact cells. Cancer Res 36:2891–2895PubMed
Nakagawa Y, Abe S, Kurata M, Hasegawa M, Yamamoto K, Inoue M, Takemura T, Suzuki K, Kitagawa M (2006) IAP family protein expression correlates with poor outcome of multiple myeloma patients in association with chemotherapy-induced overexpression of multidrug resistance genes. Am J Hematol 81:824–831CrossRefPubMed
Ng KCP, Campos EI, Martinka M, Li G (2004) XAF1 expression is significantly reduced in human melanoma. J Invest Dermatol 123:1127–1134CrossRefPubMed
Nishiyama M, Yamamoto W, Park J-S, Okamoto R, Hanaoka H, Takano H, Saito N, Matsukawa M, Shirasaka T, Kurihara M (1999) Low-dose cisplatin and 5-fluorouracil in combination canrepress increased gene expression of cellular resistance determinants to themselves. Clin Cancer Res 5:2620–2628PubMed
Pan Q-W, Zhong S-Y, Liu B-S, Liu J, Cai R, Wang Y-G, Liu X-Y, Qian C (2007a) Enhanced sensitivity of hepatocellular carcinoma cells to chemotherapy with a Smac-armed oncolytic adenovirus. Acta Pharmacol Sin 28:1996–2004CrossRefPubMed
Pan Q, Liu B, Liu J, Cai R, Wang Y, Qian C (2007b) Synergistic induction of tumor cell death by combining cisplatin with an oncolytic adenovirus carrying TRAIL. Mol Cell Biochem 304:315–323CrossRefPubMed
Qi R, Gu J, Zhang Z, Yang K, Li B, Fan J, Wang C, He Z, Qiao L, Lin Z (2006) Potent antitumor efficacy of XAF1 delivered by conditionally replicative adenovirus vector via caspase-independent apoptosis. Cancer Gene Ther 14:82–90CrossRefPubMed
Rosenberg B, Van Camp L, Krigas T (1965) Inhibition of cell division in Escherichia coli by electrolysis products from a platinum electrode. Nature 205:698–699CrossRefPubMed
Sun PH, Zhu LM, Qiao MM, Zhang YP, Jiang SH, Wu YL, Tu SP (2011) The XAF1 tumor suppressor induces autophagic cell death via upregulation of Beclin-1 and inhibition of Akt pathway. Cancer Lett 310:170–180CrossRefPubMed
Suzuki K, Fueyo J, Krasnykh V, Reynolds PN, Curiel DT, Alemany R (2001) A conditionally replicative adenovirus with enhanced infectivity shows improved oncolytic potency. Clin Cancer Res 7:120–126PubMed
Tamm I, Kornblau SM, Segall H, Krajewski S, Welsh K, Kitada S, Scudiero DA, Tudor G, Qui YH, Monks A (2000) Expression and prognostic significance of IAP-family genes in human cancers and myeloid leukemias. Clin Cancer Res 6:1796–1803PubMed
Wang Y, Huang F, Cai H, Wu Y, He G, Tan W-S (2010) The efficacy of combination therapy using adeno-associated virus-TRAIL targeting to telomerase activity and cisplatin in a mice model of hepatocellular carcinoma. J Cancer Res Clin Oncol 136:1827–1837CrossRefPubMed
Wu Y-M, Zhang K-J, Yue X-T, Wang Y-Q, Yang Y, Li G-C, Li N, Wang Y-G (2009) Enhancement of tumor cell death by combining cisplatin with an oncolytic adenovirus carrying MDA-7/IL-24. Acta Pharmacol Sin 30:467–477CrossRefPubMedCentralPubMed
Zhang ZL, Wei Guo Z, Chun Xia L, Bing Hua L, Jin Hui W, Lan Ying S, Qi Jun Q, Liu XY (2003) An armed oncolytic adenovirus system, ZD55-gene, demonstrating potent antitumoral efficacy. Cell Res 13:481–489CrossRefPubMed
Zhao L, Gu J, Dong A, Zhang Y, Zhong L, He L, Wang Y, Zhang J, Zhang Z, Huiwang J (2005) Potent antitumor activity of oncolytic adenovirus expressing mda-7/IL-24 for colorectal cancer. Hum Gene Ther 16:845–858CrossRefPubMed
Zou W, Luo C, Zhang Z, Liu J, Gu J, Pei Z, Qian C, Liu X (2004) A novel oncolytic adenovirus targeting to telomerase activity in tumor cells with potent. Oncogene 23:457–464CrossRefPubMed
Metadata
Title
Synergistic suppression effect on tumor growth of hepatocellular carcinoma by combining oncolytic adenovirus carrying XAF1 with cisplatin
Authors
Buyun Ma
Yanchun Wang
Xiumei Zhou
Panpan Huang
Rong Zhang
Tao Liu
Caixia Cui
Xinyuan Liu
Yigang Wang
Publication date
01-03-2015
Publisher
Springer Berlin Heidelberg
Published in
Journal of Cancer Research and Clinical Oncology / Issue 3/2015
Print ISSN: 0171-5216
Electronic ISSN: 1432-1335
DOI
https://doi.org/10.1007/s00432-014-1835-8

Other articles of this Issue 3/2015

Journal of Cancer Research and Clinical Oncology 3/2015 Go to the issue

Original Article - Cancer Research

Ezrin-expressing lung adenocarcinoma cells and podoplanin-positive fibroblasts form a malignant microenvironment

Original Article – Cancer Research

Classification and prediction of HCC tissues by Raman imaging with identification of fatty acids as potential lipid biomarkers

Original Article – Clinical Oncology

The oncological outcome and validation of Japan Cancer of the Prostate Risk Assessment score among men treated with primary androgen-deprivation therapy

Original Article – Clinical Oncology

Final results of a phase II trial for stereotactic body radiation therapy for patients with inoperable liver metastases from colorectal cancer

Original Article – Cancer Research

microRNA-548l is involved in the migration and invasion of non-small cell lung cancer by targeting the AKT1 signaling pathway

Original Article - Cancer Research

Targeting VEGF and interleukin-6 for controlling malignant effusion of primary effusion lymphoma
Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Reserve your place

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin
Prof. Florian Limbourg
Prof. Anoop Chauhan
Developed by: Springer Medicine
Obesity Clinical Trial Summary

At a glance: The STEP trials

Read more

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Highlights from the ACC 2024 Congress

Year in Review: Pediatric cardiology

Pediatric Cardiology Video

Watch Dr. Anne Marie Valente present the last year's highlights in pediatric and congenital heart disease in the official ACC.24 Year in Review session.

Year in Review: Pulmonary vascular disease

Cardiopulmonary Comorbidity Video

The last year's highlights in pulmonary vascular disease are presented by Dr. Jane Leopold in this official video from ACC.24.

Year in Review: Valvular heart disease

Valvular Heart Disease Video

Watch Prof. William Zoghbi present the last year's highlights in valvular heart disease from the official ACC.24 Year in Review session.

Year in Review: Heart failure and cardiomyopathies

Heart Failure Video

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.

ACC 2024 Congress Coverage

Year in Review: Heart failure and cardiomyopathies

Heart Failure Video

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.

Watch now

Semaglutide benefits people with type 2 diabetes and obesity-related heart failure

16-04-2024 Type 2 Diabetes News

Incentivised to exercise

11-04-2024 Lifestyle Modifications News

New intervention for STEMI-related cardiogenic shock

10-04-2024 Myocardial Infarction News

» View more highlights on the ACC 2024 congress hub page

Image Credits