Potent Anti-tumour Activity of a Novel Conditionally Replicating Adenovirus for Melanoma Via Inhibition of Migration and Invasion

Overview

Journal Br J Cancer

Specialty Oncology

Date 2014 Apr 10

PMID 24714752

Citations 8

Authors

G Jiang

C-S Yang

D Xu

C Sun

J-N Zheng

T-C Lei

Y-Q Liu

Affiliations

Soon will be listed here.

Abstract

Background: Conditionally replicating adenoviruses (CRAds) represent a novel class of oncological therapeutic agents. One strategy to ensure tumour targeting is to place the essential viral genes under the control of tumour-specific promoters. Ki67 has been selected as a cancer gene therapy target, as it is expressed in most malignant cells but is barely detectable in most normal cells. This study aimed to investigate the effects of a Ki67 promoter-controlled CRAd (Ki67-ZD55-IL-24) on the proliferation and apoptosis of melanoma cells.

Methods: Melanoma cells were independently treated with Ki67-ZD55-IL-24, ZD55-IL-24, Ki67-ZD55, and ZD55-EGFP. The cytotoxic potential of each treatment was assessed using cell viability measurements. Cell migration and invasion were assayed using cell migration and invasion assays. Apoptosis was assayed using the annexin V-FITC assay, western blotting, reverse transcriptase PCR (RT-PCR), haematoxylin and eosin (H&E) staining, and the TUNEL assay.

Results: Our results showed that Ki67-ZD55-IL-24 had significantly enhanced anti-tumour activity as it more effectively induced apoptosis in melanoma cells than the other agents. Ki67-ZD55-IL-24 also caused the most significant inhibition of cell migration and invasion of melanoma cells. Furthermore, apoptosis was induced more effectively in melanoma xenografts in nude mice.

Conclusions: This strategy holds promising potential for the further development of an effective approach to treat malignant melanoma.

Citing Articles

Insights into the Mechanisms of Action of MDA-7/IL-24: A Ubiquitous Cancer-Suppressing Protein.

Modi J, Roy A, Pradhan A, Kumar A, Talukdar S, Bhoopathi P Int J Mol Sci. 2022; 23(1).

PMID: 35008495 PMC: 8744595. DOI: 10.3390/ijms23010072.

Efficacy of a novel double-controlled oncolytic adenovirus driven by the Ki67 core promoter and armed with IL-15 against glioblastoma cells.

Zhang Q, Zhang J, Tian Y, Zhu G, Liu S, Liu F Cell Biosci. 2020; 10:124.

PMID: 33133514 PMC: 7592588. DOI: 10.1186/s13578-020-00485-1.

Role of the p53‑TRPM1/miR‑211‑MMP9 axis in UVB‑induced human melanocyte migration and its potential in repigmentation.

Su M, Miao F, Jiang S, Shi Y, Luo L, He X Int J Mol Med. 2020; 45(4):1017-1026.

PMID: 31985026 PMC: 7053874. DOI: 10.3892/ijmm.2020.4478.

Novel tyrosinase inhibitory peptide with free radical scavenging ability.

Shen Z, Wang Y, Guo Z, Tan T, Zhang Y J Enzyme Inhib Med Chem. 2019; 34(1):1633-1640.

PMID: 31496313 PMC: 6746264. DOI: 10.1080/14756366.2019.1661401.

Ki67 targeted strategies for cancer therapy.

Yang C, Zhang J, Ding M, Xu K, Li L, Mao L Clin Transl Oncol. 2017; 20(5):570-575.

PMID: 29058263 DOI: 10.1007/s12094-017-1774-3.

References

Pei D, Qian G, Tian H, Mou J, Li W, Zheng J . Analysis of human Ki-67 gene promoter and identification of the Sp1 binding sites for Ki-67 transcription. Tumour Biol. 2011; 33(1):257-66. DOI: 10.1007/s13277-011-0277-z. View

Rioux-Leclercq N, Turlin B, Bansard J, Patard J, Manunta A, Moulinoux J . Value of immunohistochemical Ki-67 and p53 determinations as predictive factors of outcome in renal cell carcinoma. Urology. 2000; 55(4):501-5. DOI: 10.1016/s0090-4295(99)00550-6. View

Yano S, Tazawa H, Hashimoto Y, Shirakawa Y, Kuroda S, Nishizaki M . A genetically engineered oncolytic adenovirus decoys and lethally traps quiescent cancer stem-like cells in S/G2/M phases. Clin Cancer Res. 2013; 19(23):6495-505. DOI: 10.1158/1078-0432.CCR-13-0742. View

Eriksson M, Guse K, Bauerschmitz G, Virkkunen P, Tarkkanen M, Tanner M . Oncolytic adenoviruses kill breast cancer initiating CD44+CD24-/low cells. Mol Ther. 2007; 15(12):2088-93. DOI: 10.1038/sj.mt.6300300. View

Liu E, Telem D, Warner R, Dikman A, Divino C . The role of Ki-67 in predicting biological behavior of goblet cell carcinoid tumor in appendix. Am J Surg. 2011; 202(4):400-3. DOI: 10.1016/j.amjsurg.2010.08.036. View

Zhao L, Gu J, Dong A, Zhang Y, Zhong L, He L . Potent antitumor activity of oncolytic adenovirus expressing mda-7/IL-24 for colorectal cancer. Hum Gene Ther. 2005; 16(7):845-58. DOI: 10.1089/hum.2005.16.845. View

Jiang H, Su Z, Lin J, Goldstein N, Young C, Fisher P . The melanoma differentiation associated gene mda-7 suppresses cancer cell growth. Proc Natl Acad Sci U S A. 1996; 93(17):9160-5. PMC: 38612. DOI: 10.1073/pnas.93.17.9160. View

Eberle J, Kurbanov B, Hossini A, Trefzer U, Fecker L . Overcoming apoptosis deficiency of melanoma-hope for new therapeutic approaches. Drug Resist Updat. 2007; 10(6):218-34. DOI: 10.1016/j.drup.2007.09.001. View

Yerushalmi R, Woods R, Ravdin P, Hayes M, Gelmon K . Ki67 in breast cancer: prognostic and predictive potential. Lancet Oncol. 2010; 11(2):174-83. DOI: 10.1016/S1470-2045(09)70262-1. View

10.

Zheng J, Ma T, Cao J, Sun X, Chen J, Li W . Knockdown of Ki-67 by small interfering RNA leads to inhibition of proliferation and induction of apoptosis in human renal carcinoma cells. Life Sci. 2005; 78(7):724-9. DOI: 10.1016/j.lfs.2005.05.064. View

11.

Cody J, Douglas J . Armed replicating adenoviruses for cancer virotherapy. Cancer Gene Ther. 2009; 16(6):473-88. PMC: 2683179. DOI: 10.1038/cgt.2009.3. View

12.

Beresford M, Wilson G, Makris A . Measuring proliferation in breast cancer: practicalities and applications. Breast Cancer Res. 2006; 8(6):216. PMC: 1797032. DOI: 10.1186/bcr1618. View

13.

Jiang G, Jiang A, Cheng Q, Tian H, Li L, Zheng J . A dual-regulated oncolytic adenovirus expressing interleukin-24 sensitizes melanoma cells to temozolomide via the induction of apoptosis. Tumour Biol. 2013; 34(2):1263-71. DOI: 10.1007/s13277-013-0701-7. View

14.

Chai L, Liu S, Mao Q, Wang D, Li X, Zheng X . A novel conditionally replicating adenoviral vector with dual expression of IL-24 and arresten inserted in E1 and the region between E4 and fiber for improved melanoma therapy. Cancer Gene Ther. 2011; 19(4):247-54. DOI: 10.1038/cgt.2011.84. View

15.

Eberle J, Fecker L, Hossini A, Kurbanov B, Fechner H . Apoptosis pathways and oncolytic adenoviral vectors: promising targets and tools to overcome therapy resistance of malignant melanoma. Exp Dermatol. 2007; 17(1):1-11. DOI: 10.1111/j.1600-0625.2007.00655.x. View

16.

Emdad L, Lebedeva I, Su Z, Gupta P, Sauane M, Dash R . Historical perspective and recent insights into our understanding of the molecular and biochemical basis of the antitumor properties of mda-7/IL-24. Cancer Biol Ther. 2009; 8(5):391-400. DOI: 10.4161/cbt.8.5.7581. View

17.

Keam B, Im S, Lee K, Han S, Oh D, Kim J . Ki-67 can be used for further classification of triple negative breast cancer into two subtypes with different response and prognosis. Breast Cancer Res. 2011; 13(2):R22. PMC: 3219180. DOI: 10.1186/bcr2834. View

18.

Cheang M, Chia S, Voduc D, Gao D, Leung S, Snider J . Ki67 index, HER2 status, and prognosis of patients with luminal B breast cancer. J Natl Cancer Inst. 2009; 101(10):736-50. PMC: 2684553. DOI: 10.1093/jnci/djp082. View

19.

Eager R, Harle L, Nemunaitis J . Ad-MDA-7; INGN 241: a review of preclinical and clinical experience. Expert Opin Biol Ther. 2008; 8(10):1633-43. DOI: 10.1517/14712598.8.10.1633. View

20.

Bischoff J, Kirn D, Williams A, Heise C, Horn S, Muna M . An adenovirus mutant that replicates selectively in p53-deficient human tumor cells. Science. 1996; 274(5286):373-6. DOI: 10.1126/science.274.5286.373. View