Mycoplasma hyorhinis reduces sensitivity of human lung carcinoma cells to Nutlin-3 and promotes their malignant phenotype.

Autor: Boyarskikh UA; Laboratory of Pharmacogenomics, Institute of Chemical Biology and Fundamental Medicine, 8 Lavrentjev Avenue, Novosibirsk, 630090, Russia., Shadrina AS; Laboratory of Pharmacogenomics, Institute of Chemical Biology and Fundamental Medicine, 8 Lavrentjev Avenue, Novosibirsk, 630090, Russia. weiner.alexserg@gmail.com.; Novosibirsk State University, 2 Pirogova Street, Novosibirsk, 630090, Russia. weiner.alexserg@gmail.com., Smetanina MA; Laboratory of Pharmacogenomics, Institute of Chemical Biology and Fundamental Medicine, 8 Lavrentjev Avenue, Novosibirsk, 630090, Russia.; Novosibirsk State University, 2 Pirogova Street, Novosibirsk, 630090, Russia., Tsepilov YA; Novosibirsk State University, 2 Pirogova Street, Novosibirsk, 630090, Russia.; Institute of Cytology and Genetics, 10 Lavrentjev Avenue, Novosibirsk, 630090, Russia., Oscorbin IP; Laboratory of Pharmacogenomics, Institute of Chemical Biology and Fundamental Medicine, 8 Lavrentjev Avenue, Novosibirsk, 630090, Russia.; Novosibirsk State University, 2 Pirogova Street, Novosibirsk, 630090, Russia., Kozlov VV; Novosibirsk Regional Clinical Oncological Center, 2 Plakhotnogo Street, Novosibirsk, 630108, Russia., Kel AE; Laboratory of Pharmacogenomics, Institute of Chemical Biology and Fundamental Medicine, 8 Lavrentjev Avenue, Novosibirsk, 630090, Russia.; Department of Research and Development, geneXplain GmbH, Am Exer 10b, 38302, Wolfenbüttel, Germany., Filipenko ML; Laboratory of Pharmacogenomics, Institute of Chemical Biology and Fundamental Medicine, 8 Lavrentjev Avenue, Novosibirsk, 630090, Russia.; Novosibirsk State University, 2 Pirogova Street, Novosibirsk, 630090, Russia.
Jazyk: angličtina
Zdroj: Journal of cancer research and clinical oncology [J Cancer Res Clin Oncol] 2018 Jul; Vol. 144 (7), pp. 1289-1300. Date of Electronic Publication: 2018 May 08.
DOI: 10.1007/s00432-018-2658-9
Abstrakt: Purpose: MDM2 inhibitors are promising anticancer agents that induce cell cycle arrest and tumor cells death via p53 reactivation. We examined the influence of Mycoplasma hyorhinis infection on sensitivity of human lung carcinoma cells NCI-H292 to MDM2 inhibitor Nutlin-3. In order to unveil possible mechanisms underlying the revealed effect, we investigated gene expression changes and signal transduction networks activated in NCI-H292 cells in response to mycoplasma infection.
Methods: Sensitivity of NCI-Н292 cells to Nutlin-3 was estimated by resazurin-based cell viability assay. Genome-wide transcriptional profiles of NCI-H292 and NCI-Н292 Myc.h cell lines were determined using Illumina Human HT-12 v3 Expression BeadChip. Search for key transcription factors and key node molecules was performed using the geneXplain platform. Ability for anchorage-independent growth was tested by soft agar colony formation assay.
Results: NCI-Н292 Myc.h cells were shown to be 1.5- and 5.2-fold more resistant to killing by Nutlin-3 at concentrations of 15 and 30 µM than uninfected NCI-Н292 cells (P < 0.05 and P < 0.001, respectively). Transcriptome analysis revealed differential expression of multiple genes involved in cancer progression and metastasis as well as epithelial-mesenchymal transition (EMT). Moreover, we have shown experimentally that NCI-Н292 Myc.h cells were more capable of growing and dividing without binding to a substrate. The most likely mechanism explaining the observed changes was found to be TLR4- and IL-1b-mediated activation of NF-κB pathway.
Conclusions: Our results provide evidence that mycoplasma infection is an important factor modulating the effect of MDM2 inhibitors on cancer cells and is able to induce EMT-related changes.
Databáze: MEDLINE
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