title: Inhibition of p90 ribosomal S6 kinase attenuates cell migration and proliferation of the human lung adenocarcinoma through phospho-GSK-3β and osteopontin.
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.
authors.affiliation: College of Pharmacy, Qatar University, P.O. Box 2713, Doha, Qatar.
authors.forename: Nabeel
authors.initials: N
authors.lastname: Abdulrahman
authors.affiliation: College of Pharmacy, Qatar University, P.O. Box 2713, Doha, Qatar.
authors.forename: Maiy
authors.initials: M
authors.lastname: Jaballah
authors.affiliation: College of Pharmacy, Qatar University, P.O. Box 2713, Doha, Qatar.
authors.forename: Noufira
authors.initials: N
authors.lastname: Poomakkoth
authors.affiliation: College of Pharmacy, Qatar University, P.O. Box 2713, Doha, Qatar.
authors.forename: Sadaf
authors.initials: S
authors.lastname: Riaz
authors.affiliation: College of Pharmacy, Qatar University, P.O. Box 2713, Doha, Qatar.
authors.forename: Somaia
authors.initials: S
authors.lastname: Abdelaziz
authors.affiliation: College of Pharmacy, Qatar University, P.O. Box 2713, Doha, Qatar.
authors.forename: Aya
authors.initials: A
authors.lastname: Issa
authors.affiliation: College of Pharmacy, Qatar University, P.O. Box 2713, Doha, Qatar. fatima.mraiche@qu.edu.qa.
authors.forename: Fatima
authors.initials: F
authors.lastname: Mraiche
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D002465:Cell Movement / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D000071679:Glycogen Synthase Kinase 3 beta / Q000096:biosynthesis* / Q000235:genetics; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D053495:Osteopontin / Q000096:biosynthesis* / Q000235:genetics; D011621:Pteridines / Q000494:pharmacology*; D038744:Ribosomal Protein S6 Kinases, 90-kDa / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism
chemical_list: C516541:BI D1870; D009363:Neoplasm Proteins; D011621:Pteridines; C506895:SPP1 protein, human; D053495:Osteopontin; C000605506:GSK3B protein, human; D000071679:Glycogen Synthase Kinase 3 beta; D038744:Ribosomal Protein S6 Kinases, 90-kDa
keywords: Anti-apoptosis; Cell migration; Cell proliferation; Glycogen synthase kinase-3β; Lung adenocarcinoma; Osteopontin; p90 Ribosomal S6 kinase