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Liver Cancer Cell Lines Treated with Doxorubicin under Normoxia and Hypoxia: Cell Viability and Oncologic Protein Profile
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmacy.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmacy.ORCID iD: 0000-0003-4318-6039
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2019 (English)In: Cancers, ISSN 2072-6694, Vol. 11, no 7, article id 1024Article in journal (Refereed) Published
Abstract [en]

Hepatocellular carcinoma is often treated with a combination of doxorubicin and embolization, exposing it to high concentrations and hypoxia. Separation of the possible synergistic effect of this combination in vivo is difficult. Here, treatment with doxorubicin, under hypoxia or normoxia in different liver cancer cell lines, was evaluated. Liver cancer cells HepG2, Huh7, and SNU449 were exposed to doxorubicin, hypoxia, or doxorubicin + hypoxia with different duration. Treatment response was evaluated with cell viability, apoptosis, oxidative stress, and summarized with IC50. The protein profile of a 92-biomarker panel was analyzed on cells treated with 0 or 0.1 mu M doxorubicin during 6 or 72 h, under normoxia or hypoxia. Hypoxia decreased viability of HepG2 and SNU499. HepG2 was least and SNU449 most tolerant to doxorubicin treatment. Cytotoxicity of doxorubicin increased over time in HepG2 and Huh7. The combination of doxorubicin + hypoxia affected the cells differently. Normalized protein expression was lower for HepG2 than Huh7 and SNU449. Hierarchical clustering separated HepG2 from Huh7 and SNU449. These three commonly used cell lines have critically different responses to chemotherapy and hypoxia, which was reflected in their different protein expression profile. These different responses suggest that tumors can respond differently to the combination of local chemotherapy and embolization.

Place, publisher, year, edition, pages
MDPI , 2019. Vol. 11, no 7, article id 1024
Keywords [en]
IC50, doxorubicin, liver cancer, cell lines, hypoxia, normoxia
National Category
Cancer and Oncology
Identifiers
URN: urn:nbn:se:uu:diva-395927DOI: 10.3390/cancers11071024ISI: 000479322800134PubMedID: 31330834OAI: oai:DiVA.org:uu-395927DiVA, id: diva2:1366617
Funder
Swedish Cancer Society, CAN2018/602Swedish Cancer Society, CAN2017/518Swedish Cancer Society, CAN2013/1273Swedish Research Council, 2018-03301Swedish Society for Medical Research (SSMF), S17-0092Available from: 2019-10-30 Created: 2019-10-30 Last updated: 2019-10-30Bibliographically approved

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Dubbelboer, Ilse RPavlovic, NatasaHeindryckx, FemkeSjögren, ErikLennernäs, Hans
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