Kev tshawb fawb hauv nas thiab tib neeg lub hlwb piav qhia txog kev rov ua haujlwm ntawm cov qog nqaij hlav tseem ceeb uas siv cov zaub extract yog li muab lub tswv yim zoo rau cancer kev kho mob
cancer yog qhov thib ob ua rau muaj neeg tuag thoob ntiaj teb. Hauv kev mob qog noj ntshav, ntau yam kev hloov pauv caj ces thiab epigenetic hloov pauv tau los yog tau txais somatically. Cov kev hloov pauv no koom nrog kev txhim kho mob qog noj ntshav yog ob hom sib txawv - (a) ua kom lossis 'nce hauv kev ua haujlwm' ntawm cov cellular oncogenes thiab (b) inactivation lossis 'tsis ua haujlwm' ntawm cov qog suppressor noob. Lub Pob Tawb suppressor noob feem ntau inhibit cell proliferation thiab qog kev loj hlob. Yog hais tias lawv tau deactivated, tsis zoo regulators ntawm cell proliferation yog ploj lawm thiab qhov no ua rau txawv txav proliferation ntawm qog hlwb. Reactivation ntawm qog suppressors ua ib lub tswv yim zoo rau kev kho tib neeg Cancer tau tshawb fawb tab sis tsis tau tshawb pom ntau npaum li kev tshawb fawb txog inhibition ntawm oncogenic proteins.
Cov qog nqaij hlav muaj zog hu ua PTEN yog qhov feem ntau hloov pauv, tshem tawm, tswj tsis tau lossis ntsiag to cov noob hauv tib neeg cov qog nqaij hlav. PTEN yog ib qho phosphatase uas ua haujlwm zoo li lub dimer ntawm cov plasma membrane. Yog tias PTEN kev hloov pauv tau txais txiaj ntsig ces nws tuaj yeem ua rau cov tsos mob xws li raug rau cancer thiab kev loj hlob tsis xws luag. Cov qog hlwb pom cov qib qis ntawm PTEN. Kev kho kom rov zoo li qub ntawm PTEN hauv cov qog nqaij hlav qog noj ntshav tuaj yeem tso cai rau PTEN gene txuas ntxiv nws cov qog nqaij hlav. Nws paub tias PTEN dimer tsim thiab nws cov neeg ua haujlwm ntawm daim nyias nyias yog qhov tseem ceeb rau nws txoj haujlwm, txawm li cas los xij, qhov tseeb molecular mechanisms ntawm qhov no tseem tsis tau paub.
Kev tshawb fawb luam tawm hauv Science Lub Tsib Hlis 17, 2019 piav qhia txog txoj hauv kev tshiab uas cuam tshuam nrog PTEN uas yog tus tswj xyuas cov qog loj hlob thiab tseem ceeb rau kev loj hlob ntawm qog noj ntshav. Cov kws tshawb fawb tau kawm txog cov noob hu ua WWP1 uas paub tias ua lub luag haujlwm tseem ceeb hauv kev txhim kho qog noj ntshav thiab tsim cov enzyme ubiquitin E3 ligase. Cov enzyme no yog PTEN interacting protein uas inhibits qog suppressive kev ua ntawm PTEN los ntawm suppressing PTEN lub dimerization, membrane recruitment thiab yog li nws cov dej num. WWP1 yog genetic augmented nyob rau hauv ntau cov qog nqaij hlav nrog rau lub mis, prostate thiab daim siab. Tom qab tshawb xyuas qhov enzyme 3-dimensional qauv, cov kws tshawb nrhiav shortlisted ib tug me me molecule hu ua indole-3-carbinol (I3C) uas yuav inhibit qhov kev ua ntawm no enzyme. I3C, ib tug natural compound, yog ib qho khoom xyaw ntawm broccoli thiab lwm yam cruciferous zaub uas muaj xws li zaub qhwv, zaub qhwv, kale thiab brussels sprouts. Nws paub zoo tias cov zaub zoo li no muaj txiaj ntsig zoo ntxiv rau ib tus neeg noj zaub mov thiab lawv cov kev noj haus yav dhau los tau txuas rau kev txo qis ntawm kev mob qog noj ntshav.
Lub compound I3C tau muab rau cov nas mob qog noj ntshav (tus qauv nas ntawm prostate cancer) thiab rau hauv tib neeg cov kab ntawm tes thiab nws tau pom tias I3C inhibited kev ua ntawm WWP1 los ntawm depleting nws. Qhov no ua rau cov qog nqaij hlav rov qab muaj zog ntawm PTEN. I3C yog li lub ntuj pharmacological inhibitor ntawm WWP1 uas tuaj yeem ua rau PTEN reactivation. WWP1 tau tshwm sim los ua MYC lub hom phiaj ncaj qha (protooncogene) rau MYC tsav cov qog nqaij hlav lossis tsim cov qog. Txoj kev tshawb no tau pom tias kev cuam tshuam ntawm WWP1 yog txaus los kho PTEN cov qog nqaij hlav.
Tej zaum nws yuav tsis muaj peev xwm ua kom tau cov txiaj ntsig tiv thaiv kab mob no los ntawm kev haus broccoli thiab lwm yam zaub cruciferous ua zaub mov vim tias muaj ntau ntau ntawm kev noj txhua hnub yuav xav tau. Kev tshawb nrhiav ntxiv yuav tsum tau tsom mus rau kev kawm txog kev ua haujlwm ntawm WWP1 thiab txhim kho nws cov inhibitors raws li txoj kev tshawb fawb tam sim no tsim kom muaj kev cuam tshuam ntawm WWP1-PTEN txoj hauv kev tau cog lus thaum muaj cov qog-tsav MYC overexpression lossis PTEN kev ua haujlwm tsis zoo. Txoj kev tshawb fawb tam sim no ua rau txoj kev tshiab cancer Kev kho mob siv cov qog suppressor reactivation mus kom ze.
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{Koj tuaj yeem nyeem cov ntawv tshawb fawb thawj zaug los ntawm nyem rau ntawm DOI qhov txuas tau muab hauv qab no hauv cov npe ntawm cov khoom raug suav nrog}
Qhov (s)
Li Y. et al. 2019. Reactivation of PTEN qog suppressor for cancer treatment by inhibition of a MYC-WWP1 inhibitory pathway. Science, 364 (6441). https://doi.org/10.1126/science.aau0159
