Targeting acute hypoxic cancer cells by doxorubicin-immunoliposomes directed by monoclonal antibodies specific to RON receptor tyrosine kinase

Cancer Chemotherapy and Pharmacology
Sunny GuinMing-Hai Wang

Abstract

Hypoxia contributes to acquired drug resistance in various cancer cells. The underlying mechanism is cellular insensitivity regulated by hypoxia-inducible factors (HIF), which impairs drug uptake, transport, and metabolism. The current study determines anti-RON antibody-directed cytotoxicity of doxorubicin (Dox)-immunoliposomes (IL) in hypoxic colon cancer cells. Cells were cultured under hypoxia (1% O(2), 5% CO(2), and 96% N(2)) for 24 h. Dox-loaded IL were formulated followed by post-insertion of monoclonal antibody Zt/g4 specific to RON. Western blotting was used to detect HIF-1α and RON expression. Cellular uptake of Zt/g4-conjugated IL was determined by confocal and internalization assays. Cell viability was assessed by the MTT assay. RON and HIF-1α expression were observed in hypoxic colon HCT116 and SW620 cells. Resistance to Dox-induced cytotoxicity was acquired in hypoxic cells with increased IC(50) values. However, acquired resistance was attenuated by Zt/g4-directed Dox-IL, which displays increased cytotoxic activities. IL binding and uptake revealed that hypoxic RON expression is functional, which mediates high levels of Zt/g4-Dox-IL binding and cytoplasmic internalization. Zt/g4-Dox-IL is effective in killing hypox...Continue Reading

References

Dec 6, 2000·British Journal of Cancer·L H Patterson, S R McKeown
Mar 21, 2002·Nature Reviews. Cancer·Adrian L Harris
Mar 22, 2002·Nature Reviews. Cancer·P Carter
Apr 2, 2002·Neoplasia : an International Journal for Oncology Research·Toru ShibataJ Martin Brown
Sep 18, 2003·Nature Reviews. Cancer·Gregg L Semenza
Apr 10, 2004·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Kenji Yokoi, Isaiah J Fidler
Jun 2, 2004·Nature Reviews. Cancer·J Martin Brown, William R Wilson
Mar 25, 2005·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Wen-Ying LeeHow-Ran Guo
Apr 14, 2005·Annals of Surgical Oncology·E Ramsay CampLee M Ellis
Nov 23, 2006·Current Topics in Developmental Biology·Michele M Hickey, M Celeste Simon
Mar 30, 2007·Nature Clinical Practice. Oncology·Alejandro D Ricart, Anthony W Tolcher
Apr 4, 2007·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Naz Chaudary, Richard P Hill
Apr 26, 2007·Proceedings of the National Academy of Sciences of the United States of America·Alana L WelmJ Michael Bishop
Sep 27, 2007·Journal of the National Cancer Institute·Olivier TrédanIan F Tannock
Feb 9, 2008·Cell Death and Differentiation·E B Rankin, A J Giaccia
Mar 5, 2008·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Kwangjae ChoDong M Shin
Mar 15, 2008·Cancer Research·Chitta Ranjan PatraDebabrata Mukhopadhyay
Jul 16, 2008·Advances in Cancer Research·Purnima K WaghSusan E Waltz
Nov 8, 2008·European Journal of Cancer : Official Journal for European Organization for Research and Treatment of Cancer (EORTC) [and] European Association for Cancer Research (EACR)·Manuela Milani, Adrian L Harris
Feb 10, 2009·Anti-cancer Agents in Medicinal Chemistry·Isabelle Dussault, Steven F Bellon
Mar 3, 2009·Nature Medicine·Yi WangMichael Ohh
May 12, 2009·Biochemical Pharmacology·Beverly A Teicher
Jun 13, 2009·Current Molecular Medicine·Sara RockwellVan Thuc Vu

❮ Previous
Next ❯

Citations

Sep 4, 2012·Cancer Immunology, Immunotherapy : CII·Ahmad TradJoachim Grötzinger
Jun 25, 2014·Frontiers in Pharmacology·Susan Hua
Nov 5, 2016·Journal of Cancer Research and Clinical Oncology·Omid ZareiSiavoush Dastmalchi
Jun 26, 2013·Nature Reviews. Cancer·Hang-Ping YaoMing-Hai Wang
Aug 23, 2020·International Journal of Molecular Sciences·Alberto JuanCarlos Alonso-Moreno
Oct 9, 2014·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Liang FengMing-Hai Wang
Jun 8, 2021·World Journal of Gastroenterology : WJG·Shao-Long ChenHang-Ping Yao

❮ Previous
Next ❯

Related Concepts

Related Feeds

Cancer Metabolism

In order for cancer cells to maintain rapid, uncontrolled cell proliferation, they must acquire a source of energy. Cancer cells acquire metabolic energy from their surrounding environment and utilize the host cell nutrients to do so. Here is the latest research on cancer metabolism.