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Open AccessArticle

Liver Cancer Cell Lines Treated with Doxorubicin under Normoxia and Hypoxia: Cell Viability and Oncologic Protein Profile

1
Department of Pharmacy, Uppsala University, Box 580, 751 23 Uppsala, Sweden
2
Department of Medical Cell Biology, Uppsala University, Box 571, 751 23 Uppsala, Sweden
*
Author to whom correspondence should be addressed.
Cancers 2019, 11(7), 1024; https://doi.org/10.3390/cancers11071024
Received: 3 July 2019 / Revised: 9 July 2019 / Accepted: 17 July 2019 / Published: 20 July 2019
(This article belongs to the Special Issue Hepatocellular Cancer Treatment)
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 µM 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. View Full-Text
Keywords: IC50; doxorubicin; liver cancer; cell lines; hypoxia; normoxia IC50; doxorubicin; liver cancer; cell lines; hypoxia; normoxia
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MDPI and ACS Style

Dubbelboer, I.R.; Pavlovic, N.; Heindryckx, F.; Sjögren, E.; Lennernäs, H. Liver Cancer Cell Lines Treated with Doxorubicin under Normoxia and Hypoxia: Cell Viability and Oncologic Protein Profile. Cancers 2019, 11, 1024.

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