Effect of cell microenvironment on the drug sensitivity of hepatocellular cancer cells
| Autor: | Gim Hwa Tan, Sheng Chun Chang, Richie Soong, Mohd Feroz Mohd Omar, Daniel Q. Huang, Min Ji Han, Benny Tang, Bhaskar Bhattacharya, Sarah Hong Hui Low, Yock Young Dan, Sanamerjit Singh, Joey Sze Yun Lim |
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| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Mitochondrial DNA Metabolite Cell cycle Biology glycolysis Phenotype drug development microenvironment 03 medical and health sciences chemistry.chemical_compound 030104 developmental biology 0302 clinical medicine Oncology chemistry Cell culture 030220 oncology & carcinogenesis Gene expression Cancer research Glycolysis Gene Research Paper |
| Zdroj: | Oncotarget |
| ISSN: | 1949-2553 |
| Popis: | The native hepatocellular cancer (HCC) microenvironment is characterized by more hypoxic, hypoglycemic, and acidic conditions than those used in standard cell culture. This study aimed to investigate whether HCC cells cultured in more native conditions have an altered phenotype and drug sensitivity compared to those cultured in standard conditions. Six HCC cell lines were cultured in "standard" (21% O2, 25 mM glucose) or more "native" (1% O2, 5 mM glucose, 10 mM lactate) conditions. Cells were assessed for growth rates, cell cycle distribution, relevant metabolite and protein levels, genome-wide gene expression, mitochondrial DNA sequence and sensitivity to relevant drugs. Many differences in cellular and molecular phenotypes and drug sensitivity were observed between the cells. HCC cells cultured in native conditions had slower doubling times, increased HK2 and GLUT, lower PHDA and ATP levels, and mutations in mitochondrial DNA. Thirty-one genes, including the hypoxia-associated NDRG1, were differentially expressed between the cells. HCC patients in The Cancer Genome Atlas (TCGA) with tumors with a high score based on these 31 genes had a poorer prognosis than those with a low score (p = 0.002). From 90 comparisons of drug sensitivity, increased resistance and sensitivity for cells cultured in native conditions was observed in 14 (16%) and 8 (9%) comparisons respectively. In conclusion, cells cultured in more native conditions can have a more glycolytic and aggressive phenotype and varied drug sensitivity to those cultured in standard conditions, and may provide new insights to understanding tumor biology and drug development. |
| Databáze: | OpenAIRE |
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