Matches in SemOpenAlex for { <https://semopenalex.org/work/W1972264288> ?p ?o ?g. }
- W1972264288 endingPage "406" @default.
- W1972264288 startingPage "397" @default.
- W1972264288 abstract "Objectives Gefitinib, a quinazoline-derived tyrosine kinase inhibitor, has anti-tumor activity in vivo and in vitro. Human MutS homologue-2 (MSH2) plays a central role in promoting genetic stability by correcting DNA replication errors. The present study investigated the effects of p38 mitogen-activated protein kinase (MAPK) signal on gefitinib-induced MSH2 expression in two human non-small cell lung squamous cancer cell lines. Materials and methods After the gefitinib treatment, the expressions of MSH2 mRNA were determined by real-time PCR and RT-PCR analysis. Protein levels of MSH2, phospho-MKK3/6, phospho-p38 MAPK were determined by Western blot analysis. We used specific MSH2, and p38 MAPK small interfering RNA to examine the role of p38 MAPK-MSH2 signal in regulating the chemosensitivity of gefitinib. Cell viability was assessed by MTS assay, trypan blue exclusion, and colony-forming ability assay. Results Exposure of gefitinib increased MSH2 protein and mRNA levels, which was accompanied by MKK3/6-p38 MAPK activation in H520 and H1703 cells. Moreover, blocking p38 MAPK activation by SB202190 significantly decreased gefitinib-induced MSH2 expression by increasing mRNA and protein instability. In contrast, enhancing p38 activation using constitutively active MKK6 (MKK6E) increased MSH2 protein and mRNA levels. Specific inhibition of MSH2 expression by siRNA enhanced gefitinib-induced cytotoxicity. Metformin, an anti-diabetic drug, might reduce cancer risk. In human lung squamous cancer cells, metformin decreased gefitinib-induced MSH2 expression and augmented the cytotoxic effect and growth inhibition by gefitinib. Transient expression of MKK6E or HA-p38 MAPK vector could abrogate metformin and gefitinib-induced synergistic cytotoxic effect in H520 and H1703 cells. Conclusion Together, down-regulation of MSH2 expression can be a possible strategy to enhance the sensitivity of gefitinib to human lung squamous cancer cells." @default.
- W1972264288 created "2016-06-24" @default.
- W1972264288 creator A5018293901 @default.
- W1972264288 creator A5024591142 @default.
- W1972264288 creator A5031101659 @default.
- W1972264288 creator A5031475129 @default.
- W1972264288 creator A5039887714 @default.
- W1972264288 creator A5041183081 @default.
- W1972264288 creator A5045521650 @default.
- W1972264288 creator A5054453758 @default.
- W1972264288 creator A5056471537 @default.
- W1972264288 creator A5056680093 @default.
- W1972264288 creator A5067312257 @default.
- W1972264288 creator A5083183162 @default.
- W1972264288 date "2013-12-01" @default.
- W1972264288 modified "2023-10-17" @default.
- W1972264288 title "Inhibition of p38 MAPK-dependent MutS homologue-2 (MSH2) expression by metformin enhances gefitinib-induced cytotoxicity in human squamous lung cancer cells" @default.
- W1972264288 cites W1534408084 @default.
- W1972264288 cites W1707773433 @default.
- W1972264288 cites W1954440802 @default.
- W1972264288 cites W1965909642 @default.
- W1972264288 cites W1966717845 @default.
- W1972264288 cites W1968363114 @default.
- W1972264288 cites W1971146179 @default.
- W1972264288 cites W1978901032 @default.
- W1972264288 cites W1979766088 @default.
- W1972264288 cites W1982449999 @default.
- W1972264288 cites W1983704426 @default.
- W1972264288 cites W1987334928 @default.
- W1972264288 cites W1990063646 @default.
- W1972264288 cites W1992257057 @default.
- W1972264288 cites W1994504180 @default.
- W1972264288 cites W2005274511 @default.
- W1972264288 cites W2013032516 @default.
- W1972264288 cites W2016867284 @default.
- W1972264288 cites W2021279506 @default.
- W1972264288 cites W2037074384 @default.
- W1972264288 cites W2037898576 @default.
- W1972264288 cites W2038905538 @default.
- W1972264288 cites W2043696829 @default.
- W1972264288 cites W2046503553 @default.
- W1972264288 cites W2047083378 @default.
- W1972264288 cites W2047688922 @default.
- W1972264288 cites W2049938167 @default.
- W1972264288 cites W2061035943 @default.
- W1972264288 cites W2064047613 @default.
- W1972264288 cites W2075637141 @default.
- W1972264288 cites W2085331940 @default.
- W1972264288 cites W2093664485 @default.
- W1972264288 cites W2096731080 @default.
- W1972264288 cites W2105341103 @default.
- W1972264288 cites W2108058238 @default.
- W1972264288 cites W2110627805 @default.
- W1972264288 cites W2115325946 @default.
- W1972264288 cites W2134430835 @default.
- W1972264288 cites W2135617839 @default.
- W1972264288 cites W2136932457 @default.
- W1972264288 cites W2138178697 @default.
- W1972264288 cites W2138584103 @default.
- W1972264288 cites W2141798197 @default.
- W1972264288 cites W2152407075 @default.
- W1972264288 cites W2153534791 @default.
- W1972264288 cites W2168332826 @default.
- W1972264288 cites W2236524872 @default.
- W1972264288 cites W2314716959 @default.
- W1972264288 cites W4245367233 @default.
- W1972264288 doi "https://doi.org/10.1016/j.lungcan.2013.09.011" @default.
- W1972264288 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/24138903" @default.
- W1972264288 hasPublicationYear "2013" @default.
- W1972264288 type Work @default.
- W1972264288 sameAs 1972264288 @default.
- W1972264288 citedByCount "20" @default.
- W1972264288 countsByYear W19722642882014 @default.
- W1972264288 countsByYear W19722642882016 @default.
- W1972264288 countsByYear W19722642882017 @default.
- W1972264288 countsByYear W19722642882018 @default.
- W1972264288 countsByYear W19722642882019 @default.
- W1972264288 countsByYear W19722642882020 @default.
- W1972264288 countsByYear W19722642882021 @default.
- W1972264288 countsByYear W19722642882022 @default.
- W1972264288 countsByYear W19722642882023 @default.
- W1972264288 crossrefType "journal-article" @default.
- W1972264288 hasAuthorship W1972264288A5018293901 @default.
- W1972264288 hasAuthorship W1972264288A5024591142 @default.
- W1972264288 hasAuthorship W1972264288A5031101659 @default.
- W1972264288 hasAuthorship W1972264288A5031475129 @default.
- W1972264288 hasAuthorship W1972264288A5039887714 @default.
- W1972264288 hasAuthorship W1972264288A5041183081 @default.
- W1972264288 hasAuthorship W1972264288A5045521650 @default.
- W1972264288 hasAuthorship W1972264288A5054453758 @default.
- W1972264288 hasAuthorship W1972264288A5056471537 @default.
- W1972264288 hasAuthorship W1972264288A5056680093 @default.
- W1972264288 hasAuthorship W1972264288A5067312257 @default.
- W1972264288 hasAuthorship W1972264288A5083183162 @default.
- W1972264288 hasBestOaLocation W19722642882 @default.
- W1972264288 hasConcept C121608353 @default.
- W1972264288 hasConcept C126322002 @default.
- W1972264288 hasConcept C153911025 @default.