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Article: IPA-3 inhibits the growth of liver cancer cells by suppressing PAK1 and NF-kB activation

TitleIPA-3 inhibits the growth of liver cancer cells by suppressing PAK1 and NF-kB activation
Authors
Issue Date2013
Citation
PLOS ONE, 2013, v. 8 n. 7, p. e68843 How to Cite?
AbstractHepatocellular carcinoma (HCC) is one of the major malignancies worldwide and is associated with poor prognosis due to the high incidences of metastasis and tumor recurrence. Our previous study showed that overexpression of p21-activated protein kinase 1 (PAK1) is frequently observed in HCC and is associated with a more aggressive tumor behavior, suggesting that PAK1 is a potential therapeutic target in HCC. In the current study, an allosteric small molecule PAK1 inhibitor, IPA-3, was evaluated for the potential in suppressing hepatocarcinogenesis. Consistent with other reports, inhibition of PAK1 activity was observed in several human HCC cell lines treated with various dosages of IPA-3. Using cell proliferation, colony formation and BrdU incorporation assays, we demonstrated that IPA-3 treatment significantly inhibited the growth of HCC cells. The mechanisms through which IPA-3 treatment suppresses HCC cell growth are enhancement of apoptosis and blockage of activation of NF-κB. Furthermore, our data suggested that IPA-3 not only inhibits the HCC cell growth, but also suppresses the metastatic potential of HCC cells. Nude mouse xenograft assay demonstrated that IPA-3 treatment significantly reduced the tumor growth rate and decreased tumor volume, indicating that IPA-3 can suppress the in vivo tumor growth of HCC cells. Taken together, our demonstration of the potential preclinical efficacy of IPA-3 in HCC provides the rationale for cancer therapy.
Persistent Identifierhttp://hdl.handle.net/10722/185612
PubMed Central ID

 

DC FieldValueLanguage
dc.contributor.authorWong, LLYen_US
dc.contributor.authorLam, PYen_US
dc.contributor.authorWONG, YNen_US
dc.contributor.authorLai, WLen_US
dc.contributor.authorLiu, MHFen_US
dc.contributor.authorYeung, LLen_US
dc.contributor.authorChing, YPen_US
dc.date.accessioned2013-08-20T11:34:22Z-
dc.date.available2013-08-20T11:34:22Z-
dc.date.issued2013en_US
dc.identifier.citationPLOS ONE, 2013, v. 8 n. 7, p. e68843en_US
dc.identifier.urihttp://hdl.handle.net/10722/185612-
dc.description.abstractHepatocellular carcinoma (HCC) is one of the major malignancies worldwide and is associated with poor prognosis due to the high incidences of metastasis and tumor recurrence. Our previous study showed that overexpression of p21-activated protein kinase 1 (PAK1) is frequently observed in HCC and is associated with a more aggressive tumor behavior, suggesting that PAK1 is a potential therapeutic target in HCC. In the current study, an allosteric small molecule PAK1 inhibitor, IPA-3, was evaluated for the potential in suppressing hepatocarcinogenesis. Consistent with other reports, inhibition of PAK1 activity was observed in several human HCC cell lines treated with various dosages of IPA-3. Using cell proliferation, colony formation and BrdU incorporation assays, we demonstrated that IPA-3 treatment significantly inhibited the growth of HCC cells. The mechanisms through which IPA-3 treatment suppresses HCC cell growth are enhancement of apoptosis and blockage of activation of NF-κB. Furthermore, our data suggested that IPA-3 not only inhibits the HCC cell growth, but also suppresses the metastatic potential of HCC cells. Nude mouse xenograft assay demonstrated that IPA-3 treatment significantly reduced the tumor growth rate and decreased tumor volume, indicating that IPA-3 can suppress the in vivo tumor growth of HCC cells. Taken together, our demonstration of the potential preclinical efficacy of IPA-3 in HCC provides the rationale for cancer therapy.-
dc.languageengen_US
dc.relation.ispartofPLOS ONEen_US
dc.rightsCreative Commons: Attribution 3.0 Hong Kong License-
dc.titleIPA-3 inhibits the growth of liver cancer cells by suppressing PAK1 and NF-kB activationen_US
dc.typeArticleen_US
dc.identifier.emailWong, LLY: lapywong@hku.hken_US
dc.identifier.emailLam, PY: ianlam@graduate.hku.hken_US
dc.identifier.emailLai, WL: bennywll@hku.hken_US
dc.identifier.emailLiu, MHF: liumico@hku.hken_US
dc.identifier.emailChing, YP: ypching@hku.hken_US
dc.identifier.authorityChing, YP=rp00469en_US
dc.description.naturepublished_or_final_version-
dc.identifier.doi10.1371/journal.pone.0068843-
dc.identifier.pmcidPMC3716906-
dc.identifier.hkuros217631en_US
dc.identifier.volume8en_US
dc.identifier.issue7en_US
dc.identifier.spagee68843en_US
dc.identifier.epagee68843en_US

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