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Inhibition of p90 ribosomal S6 kinase attenuates cell migration and proliferation of the human lung adenocarcinoma through phospho-GSK-3β and osteopontin

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Abstract

p90 ribosomal S6 kinase (p90RSK) constitutes a family of serine/threonine kinases that have been shown to be involved in cell proliferation of various malignancies via direct or indirect effects on the cell-cycle machinery. We investigated the role of p90RSK in lung adenocarcinomas and whether the inhibition of p90RSK diminishes cancer progression. Moreover, we investigated the involvement of glycogen synthase kinase-3β (GSK-3β) and osteopontin (OPN) in the p90RSK-induced lung adenocarcinoma progression. p90RSK, OPN, and GSK-3β protein expressions were examined in the A549 human lung adenocarcinoma cell line in the presence and absence of BI-D1870 (BID), a p90RSK inhibitor. Gene expression of anti-apoptotic and pro-apoptotic markers namely Bcl2 and Bax, respectively, were studied by reverse transcription polymerase chain reaction. In addition, the A549 lung adenocarcinoma cell line was characterized for cell proliferation using the MTT assay and cell migration using the scratch migration assay. Our study revealed that total RSK1 protein expression is over expressed in the A549 human lung adenocarcinoma cell line, an effect which is significantly reduced upon pretreatment with BID (69.32 ± 12.41 % of control; P < 0.05). The inhibition of p90RSK also showed a significant suppression of cell proliferation (54.3 ± 6.73 % of control; P < 0.01) and cell migration (187.90 ± 16.10 % of control; P < 0.01). Treatment of the A549 cells with BID regressed the expression of Bcl2 mRNA (56.92 ± 6.07 % of control; P < 0.01). BID also regressed protein expression of OPN (79.57 ± 5.32 % of control; P < 0.05) and phospho-GSK-3β (73.04 ± 8.95 % of control; P < 0.05). The p90RSK has an essential role in promoting tumor growth and proliferation in non-small cell lung cancer (NSCLC). BID may serve as an alternative cancer treatment in NSCLC.

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Abbreviations

p90RSK:

p90 Ribosomal S6 kinase

GSK:

Glycogen synthase kinase

OPN:

Osteopontin

BID:

BI-D1870

NSCLC:

Non-small cell lung cancer

ERK:

Extracellular signal-regulated kinases

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Acknowledgments

This work was supported by a Qatar University Internal Grant (QU-UG2013/2014).

Author contribution

Nabeel Abdulrahman, Noufira Poomakkoth, Maiy Jaballa, Sadaf Riaz, Somaya Abdelaziz, and Aya Issa performed the research. Nabeel Abdulrahman, Noufira Poomakkoth, and Fatima Mraiche provided intellectual contributions and research assistance. Nabeel Abdulrahman and Fatima Mraiche contributed in the analysis of the data. Nabeel Abdulrahman, Noufira Poomakkoth, Maiy Jaballa and Fatima Mraiche wrote the paper.

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Authors and Affiliations

  1. College of Pharmacy, Qatar University, P.O. Box 2713, Doha, Qatar

    Nabeel Abdulrahman, Maiy Jaballah, Noufira Poomakkoth, Sadaf Riaz, Somaia Abdelaziz, Aya Issa & Fatima Mraiche

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  1. Nabeel Abdulrahman
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  2. Maiy Jaballah
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Correspondence to Fatima Mraiche.

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Abdulrahman, N., Jaballah, M., Poomakkoth, N. et al. Inhibition of p90 ribosomal S6 kinase attenuates cell migration and proliferation of the human lung adenocarcinoma through phospho-GSK-3β and osteopontin. Mol Cell Biochem 418, 21–29 (2016). https://doi.org/10.1007/s11010-016-2727-9

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