Inhibition effect of chloroquine and integrin-linked kinase knockdown on translation in melanoma cells
| Autor: | Joanna Dulińska-Litewka, Marta Zarzycka, Dorota Gil, Piotr Laidler |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
AMPK
eIF2α Melanoma Experimental Protein Serine-Threonine Kinases Article Catalysis lcsh:Chemistry Inorganic Chemistry Mice Cell Line Tumor Antineoplastic Combined Chemotherapy Protocols melanoma LC3 Autophagy Animals Autophagy-Related Protein-1 Homolog Humans Integrin-linked kinase Physical and Theoretical Chemistry RNA Small Interfering lcsh:QH301-705.5 Molecular Biology Spectroscopy PI3K/AKT/mTOR pathway Gene knockdown biology Chemistry Cell growth TOR Serine-Threonine Kinases Organic Chemistry EIF4E Chloroquine General Medicine Transfection Computer Science Applications lcsh:Biology (General) lcsh:QD1-999 eIF4E Protein Biosynthesis mTOR Cancer research biology.protein ILK Signal transduction Drug Screening Assays Antitumor |
| Zdroj: | International Journal of Molecular Sciences Volume 22 Issue 7 International Journal of Molecular Sciences, Vol 22, Iss 3682, p 3682 (2021) |
| Popis: | The twofold role of autophagy in cancer is often the therapeutic target. Numerous regulatory pathways are shared between autophagy and other molecular processes needed in tumorigenesis, such as translation or survival signaling. Thus, we have assumed that ILK knockdown should promote autophagy, and used together with chloroquine, an autophagy inhibitor, it could generate a better anticancer effect by dysregulation of common signaling pathways. Expression at the protein level was analyzed using Western Blot siRNA transfection was done for ILK. Analysis of cell signaling pathways was monitored with phospho-specific antibodies. Melanoma cell proliferation was assessed with the crystal violet test, and migration was evaluated by scratch wound healing assays. Autophagy was monitored by the accumulation of its marker, LC3-II. Our data show that ILK knockdown by siRNA suppresses melanoma cell growth by inducing autophagy through AMPK activation, and simultaneously initiates apoptosis. We demonstrated that combinatorial treatment of melanoma cells with CQ and siILK has a stronger antitumor effect than monotherapy with either of these. It generates the synergistic antitumor effects by the decrease of translation of both global and oncogenic proteins synthesis. In our work, we point to the crosstalk between translation and autophagy regulation. |
| Databáze: | OpenAIRE |
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