Scientists investigated the effects of the PI3K inhibitor LY‑294002 and AKT inhibitor MK2206 on the chemosensitivity of oxaliplatin‑resistant liver cancer cells and the molecular mechanism involved.
[Molecular Medicine Reports]
7753456 {7753456:SSITR55E} apa 50 1 162251 https://www.stemcellsciencenews.com/wp-content/plugins/zotpress/
%7B%22status%22%3A%22success%22%2C%22updateneeded%22%3Afalse%2C%22instance%22%3A%22zotpress-31b0741ce7506715c8eede768d91e7a8%22%2C%22meta%22%3A%7B%22request_last%22%3A0%2C%22request_next%22%3A0%2C%22used_cache%22%3Atrue%7D%2C%22data%22%3A%5B%7B%22key%22%3A%22SSITR55E%22%2C%22library%22%3A%7B%22id%22%3A7753456%7D%2C%22meta%22%3A%7B%22creatorSummary%22%3A%22Xu%20et%20al.%22%2C%22parsedDate%22%3A%222021-07-01%22%2C%22numChildren%22%3A0%7D%2C%22bib%22%3A%22%3Cdiv%20class%3D%5C%22csl-bib-body%5C%22%20style%3D%5C%22line-height%3A%202%3B%20padding-left%3A%201em%3B%20text-indent%3A-1em%3B%5C%22%3E%5Cn%20%20%3Cdiv%20class%3D%5C%22csl-entry%5C%22%3EXu%2C%20R.%2C%20Zhang%2C%20Y.%2C%20Li%2C%20A.%2C%20Ma%2C%20Y.%2C%20Cai%2C%20W.%2C%20Song%2C%20L.%2C%20Xie%2C%20Y.%2C%20Zhou%2C%20S.%2C%20Cao%2C%20W.%2C%20%26amp%3B%20Tang%2C%20X.%20%282021%29.%20LY%26%23x2011%3B294002%20enhances%20the%20chemosensitivity%20of%20liver%20cancer%20to%20oxaliplatin%20by%20blocking%20the%20PI3K%5C%2FAKT%5C%2FHIF%26%23x2011%3B1%26%23x3B1%3B%20pathway.%20%3Ci%3EMolecular%20Medicine%20Reports%3C%5C%2Fi%3E%2C%20%3Ci%3E24%3C%5C%2Fi%3E%281%29%2C%201%26%23x2013%3B11.%20%3Ca%20href%3D%27https%3A%5C%2F%5C%2Fdoi.org%5C%2F10.3892%5C%2Fmmr.2021.12147%27%3Ehttps%3A%5C%2F%5C%2Fdoi.org%5C%2F10.3892%5C%2Fmmr.2021.12147%3C%5C%2Fa%3E%20%3Ca%20title%3D%27Cite%20in%20RIS%20Format%27%20class%3D%27zp-CiteRIS%27%20href%3D%27https%3A%5C%2F%5C%2Fwww.stemcellsciencenews.com%5C%2Fwp-content%5C%2Fplugins%5C%2Fzotpress%5C%2Flib%5C%2Frequest%5C%2Frequest.cite.php%3Fapi_user_id%3D7753456%26amp%3Bitem_key%3DSSITR55E%27%3ECite%3C%5C%2Fa%3E%20%3C%5C%2Fdiv%3E%5Cn%3C%5C%2Fdiv%3E%22%2C%22data%22%3A%7B%22itemType%22%3A%22journalArticle%22%2C%22title%22%3A%22LY%5Cu2011294002%20enhances%20the%20chemosensitivity%20of%20liver%20cancer%20to%20oxaliplatin%20by%20blocking%20the%20PI3K%5C%2FAKT%5C%2FHIF%5Cu20111%5Cu03b1%20pathway%22%2C%22creators%22%3A%5B%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Ruyue%22%2C%22lastName%22%3A%22Xu%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Yinci%22%2C%22lastName%22%3A%22Zhang%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Amin%22%2C%22lastName%22%3A%22Li%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Yongfang%22%2C%22lastName%22%3A%22Ma%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Wenpeng%22%2C%22lastName%22%3A%22Cai%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Li%22%2C%22lastName%22%3A%22Song%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Yinghai%22%2C%22lastName%22%3A%22Xie%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Shuping%22%2C%22lastName%22%3A%22Zhou%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Weiya%22%2C%22lastName%22%3A%22Cao%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Xiaolong%22%2C%22lastName%22%3A%22Tang%22%7D%5D%2C%22abstractNote%22%3A%22Liver%20cancer%20remains%20one%20of%20the%20leading%20causes%20of%20cancer%20deaths%20worldwide.%20The%20therapeutic%20effect%20of%20oxaliplatin%20on%20liver%20cancer%20is%20often%20limited%20by%20acquired%20resistance%20of%20the%20cancer%20cells.%20Abnormal%20activation%20of%20the%20PI3K%5C%2FAKT%20pathway%20plays%20an%20important%20role%20in%20the%20acquired%20resistance%20of%20oxaliplatin.%20The%20present%20study%20investigated%20the%20effects%20of%20the%20PI3K%20inhibitor%20LY%5Cu2011294002%20and%20AKT%20inhibitor%20MK2206%20on%20the%20chemosensitivity%20of%20oxaliplatin%5Cu2011resistant%20liver%20cancer%20cells%20and%20the%20molecular%20mechanism%20involved.%20An%20oxaliplatin%5Cu2011resistant%20liver%20cancer%20cell%20line%20HepG2%3Csup%3ER%3C%5C%2Fsup%3E%20was%20developed.%20MTT%20assay%2C%20clone%20formation%20experiments%2C%20flow%20cytometry%20and%20Annexin%5Cu00a0V%5Cu2011FITC%5C%2FPI%20staining%20were%20used%20to%20determine%20the%20proliferation%2C%20cycle%20and%20apoptosis%20of%20HepG2%3Csup%3ER%3C%5C%2Fsup%3E%20cells%20when%20oxaliplatin%20was%20combined%20with%20LY%5Cu2011294002%20or%20MK2206%20treatment.%20The%20effects%20of%20LY%5Cu2011294002%20and%20MK%5Cu20112206%20on%20the%20abnormal%20activation%20of%20PI3K%5C%2FAKT%20pathway%20and%20hypoxia%20inducible%20factor%20%28HIF%29%5Cu20111%5Cu03b1%20protein%20level%20in%20HepG2%3Csup%3ER%3C%5C%2Fsup%3E%20cells%20were%20detected%20using%20western%20blotting.%20The%20results%20indicated%20that%20the%20PI3K%5C%2FAKT%20pathway%20is%20stably%20activated%20in%20HepG2%3Csup%3ER%3C%5C%2Fsup%3E%20cells.%20Compared%20with%20the%20AKT%20inhibitor%20MK2206%2C%20the%20PI3K%20inhibitor%20LY%5Cu2011294002%20more%20effectively%20downregulated%20the%20phosphorylation%20levels%20of%20p85%2C%20p110%5Cu03b1%2C%20p110%5Cu03b2%2C%20p110%5Cu03b3%20and%20AKT%20in%20the%20PI3K%5C%2FAKT%20pathway%20in%20HepG2%3Csup%3ER%3C%5C%2Fsup%3E%20cells%2C%20and%20more%20effectively%20inhibited%20the%20proliferation%20of%20the%20cells.%20LY%5Cu2011294002%20enhanced%20the%20chemotherapy%20sensitivity%20of%20HepG2R%20cells%20to%20oxaliplatin%20by%20inducing%20G%3Csub%3E0%3C%5C%2Fsub%3E%5C%2FG%3Csub%3E1%3C%5C%2Fsub%3E%5Cu00a0phase%20arrest%20and%20increasing%20the%20proportion%20of%20apoptotic%20cells.%20In%20addition%2C%20LY%5Cu2011294002%20reduced%20the%20level%20of%20HIF%5Cu20111%5Cu03b1%2C%20which%20is%20highly%20expressed%20in%20HepG2%3Csup%3ER%3C%5C%2Fsup%3E%20cells.%20It%20was%20concluded%20that%20LY%5Cu2011294002%20enhanced%20the%20chemosensitivity%20of%20liver%20cancer%20cells%20to%20oxaliplatin%20by%20inhibiting%20the%20PI3K%5C%2FAKT%20signaling%20pathway%2C%20which%20may%20be%20related%20to%20the%20inhibition%20of%20HIF%5Cu20111%5Cu03b1%20expression.%20These%20findings%20may%20have%20clinical%20significance%20for%20the%20treatment%20of%20oxaliplatin%5Cu2011resistant%20liver%20cancer.%22%2C%22date%22%3A%222021-07-01%22%2C%22language%22%3A%22%22%2C%22DOI%22%3A%2210.3892%5C%2Fmmr.2021.12147%22%2C%22ISSN%22%3A%221791-2997%22%2C%22url%22%3A%22https%3A%5C%2F%5C%2Fwww.spandidos-publications.com%5C%2F10.3892%5C%2Fmmr.2021.12147%22%2C%22deleted%22%3A1%2C%22collections%22%3A%5B%22NTMX856R%22%5D%2C%22dateModified%22%3A%222021-05-14T17%3A03%3A51Z%22%7D%7D%5D%7D
Xu, R., Zhang, Y., Li, A., Ma, Y., Cai, W., Song, L., Xie, Y., Zhou, S., Cao, W., & Tang, X. (2021). LY‑294002 enhances the chemosensitivity of liver cancer to oxaliplatin by blocking the PI3K/AKT/HIF‑1α pathway. Molecular Medicine Reports, 24(1), 1–11. https://doi.org/10.3892/mmr.2021.12147 Cite