PNC-27 30 mg

▎ PNC 27 Qauv

▎ PNC 27 Kev Tshawb Fawb

Cov ntawv thov ntawm PNC-27 yog dab tsi?

1, Kev kho mob leukemia: 

PNC-27 muaj peev xwm khi HDM-2 protein nyob rau hauv daim nyias nyias ntawm cov qog nqaij hlav cancer thiab induce tsim cytotoxic transmembrane pores. Hauv kev tshawb fawb ntawm tib neeg uas tsis yog-stem cell mob myeloid leukemia cell kab, HDM-2 tau pom tias tau qhia ntau heev hauv daim nyias nyias ntawm U937 (mob monocytic leukemia), OCI-AML3 (mob granulomonocytic leukemia), thiab HL60 (mob promyelocytic leukemia) cell.binds onNC-2 necroptosis thiab LDH (lactate dehydrogenase) tso tawm hauv 4 teev. (LDH) tso tawm hauv 4 teev. Targeting HDM-2 ntawm lub cell membrane tej zaum yuav yog ib lub tswv yim zoo rau kev kho mob leukemia.PNC-27 tau nthuav tawm cov haujlwm tseem ceeb los tiv thaiv kab mob leukemia hauv ntau cov kab mob leukemia los ntawm kev tsom Membrane HDM-2 ^[1].

2. Induces qog cell lysis

Ua raws li qhov tsis zoo peptide: 

Ntau qhov kev tshawb fawb tau pom tias PNC-27 induces qog cell lysis raws li ib tug tsis zoo peptide es tsis yog ib feem. Piv txwv li, hauv kev tshawb fawb ntawm MCF-7 cov qog nqaij hlav cancer mis thiab tsis hloov pauv MCF-10-2A mammary epithelial hlwb, cov hlwb raug kho nrog PNC-27 nrog ntsuab fluorescently sau npe amino terminus thiab liab fluorescently sau carboxy terminus. Cov txiaj ntsig tau pom qhov txawv punctate daj fluorescence ntawm cov qog nqaij hlav qog noj ntshav ntawm 30 min, qhia tias cov peptide tsis zoo nyob rau ntawm cov qog nqaij hlav qog nqaij hlav thiab nce nrog cov qog nqaij hlav cancer. Nyob rau hauv sib piv, untransformed MCF-10-2A hlwb pib pom cov xim daj membrane fluorescence, tab sis tom qab ntawd ploj mus. Tsis zoo li cov qog nqaij hlav cancer, cov hlwb tsis hloov pauv no tseem siv tau. Qhov no qhia tias PNC-27 induces membrane cleavage nyob rau hauv cov qog nqaij hlav cancer los ntawm kev ua raws li tag nrho cov peptide, tsis yog ib feem ^[2].

Kev khi rau HDM-2 los tsim cov qauv pore: 

PNC-27 muaj ib qho HDM-2-binding structural domain thiab cell-penetrating peptide (CPP) presequence, uas induces tsim cov pore lug los ntawm kev khi rau HDM-2 ntawm lub cell membrane, ua rau qog cell lysis thiab necrosis. Conformational zog xam pom tau hais tias PNC-27 tsim ib tug complex nrog HDM-2 nyob rau hauv ib tug 1: 1 piv, nrog rau qhov ua ntu zus taw tes tawm ntawm qhov complex. Immunoscanning electron microscopy kev tshawb fawb qhia pom tias muaj ntau yam 6 nm thiab 15 nm sau cov khoom kub ntawm qhov sib piv ntawm kwv yees li 1: 1 hauv cov pores ntawm cov qog nqaij hlav cancer kho nrog PNC-27, qhia tias cov complexes tseem ceeb rau cov qauv pore. Hauv qhov sib piv, tsis muaj qhov pores tau tsim los tswj, tsis hloov pauv fibroblasts kho nrog PNC-27 ^[3].

Pancreatic Cancer: 

Cov tshuaj tiv thaiv kab mob tshiab tshiab PNC-27 peptide induces necrosis ntawm tib neeg pancreatic MiaPaCa-2 qog nqaij hlav qog noj ntshav nyob rau hauv koob tshuaj, tab sis tsis muaj tshuaj lom rau lub cev li qub. Cov kev tshawb fawb tau pom tias PNC-27, thaum ua ke nrog Gemzar, tus kws khomob kws khomob siv los kho tus kabmob pancreatic, muaj cov teebmeem cytotoxic ntau dua ntawm MiaPaCa-2 hlwb dua li Gemzar lossis PNC-27 ib leeg. Qhov no tej zaum yuav yog vim qhov PNC-27-induced pores nce permeability ntawm cov qog nqaij hlav cancer rau Gemzar, tso cai ntau dua Gemzar rau lub hom phiaj mob qog noj ntshav ^[1].

Ovarian Cancer: 

Nyob rau hauv zes qe menyuam kab mob qog noj ntshav SKOV-3 thiab OVCAR-3, HDM-2 protein yog heev nthuav tawm ntawm lub cell membrane.PNC-27 co-localizes nrog HDM-2 ntawm lub cell membrane, ua rau sai cell necrosis. Nyob rau hauv sib piv, nyob rau hauv lub non-transformed tswj cell kab HUVEC, co-localization thiab cytotoxicity ntawm PNC-27 tsis tau pom vim hais tias tsawg heev membrane HDM-2 qhia ^[1].

Colon Cancer: 

PNC-27 xaiv tua kab mob qog noj ntshav hauv plab. Hauv rau txoj kab mob qog noj ntshav ntawm txoj hnyuv, PNC-27 co-localized nrog daim nyias nyias HDM-2 thiab ua rau cov cell tuag (cov qog cell necrosis, siab LDH tso tawm, membrane txuam protein V thiab cysteine ​​3 negativity) tsuas yog hauv cov qog nqaij hlav cancer. Hauv vivo, PNC-27 ua rau necrosis ntawm cov qog nodules tab sis tsis cuam tshuam rau cov nqaij ib txwm ^[1].

3. Txhim kho kev tiv thaiv qog noj ntshav

Kev khi rau Doxil: 

Nws tau pom tias PNC27 peptide, raws li lub hom phiaj ligand, tuaj yeem txhim kho qhov kev tiv thaiv qog noj ntshav ntawm Doxil hauv HDM2-zoo qog noj ntshav. Ntau qhov sib txawv ntawm PNC27 peptide tau muab tso rau hauv Doxil, thiab kev ntsuas cytometry thiab confocal tsom xam tau ua rau C26 mob qog noj ntshav (HDM2-zoo) thiab B16F0 melanoma (HDM2-negative) hlwb. Cov txiaj ntsig tau pom tias PNC27-Doxil tau nthuav tawm cov cellular uptake thiab cytotoxicity hauv C26 hlwb, thaum cov txiaj ntsig no tsis tau pom hauv B16F0 hlwb. Piv txwv li, PNC27-Doxil (100 PNC27 peptide) ua rau muaj txiaj ntsig zoo ntawm Doxil yam tsis muaj kev cuam tshuam rau nws cov biodistribution hauv C26 qog ^[4].

4. Synergistic kho mob ntawm zes qe menyuam nrog paclitaxel

Paclitaxel yog siv dav hauv kev kho mob gynecological malignancies, tab sis nws tsom cov qog hlwb hauv M theem ntawm lub voj voog ntawm tes, nrog rau cov hlwb hauv lwm theem tseem muaj sia nyob thiab muaj peev xwm ua rau qog rov ua dua.PNC-27 yog peptide synthesized los ntawm amino acids nyob rau hauv P53-MDM-2 binding cell pendent kab uas tua kab mob ntau yam. Cov qog nqaij hlav zes qe menyuam ID8 raug rau paclitaxel tau pom tias muaj kev qhia ntau ntxiv ntawm MDM-2 thiab nce rhiab heev rau PNC-27.Cov nyhuv cytotoxic ntawm PNC-27 yog nyob ntawm nws txoj kev khi rau MDM-2, thiab thaiv MDM-2 inhibits kev tua ntawm PNC-27. Cov duab heterodrug ntawm cov koob tshuaj sib xyaw ua ke tau sib koom ua ke, qhia txog kev sib koom ua ke ntawm PNC-27 thiab paclitaxel ^[5] . Nyob rau hauv tus qauv intraperitoneal ntawm zes qe menyuam qog noj ntshav (ID8), qhov sib ntxiv ntawm PNC-27 rau kev tswj hwm paclitaxel txhua lub limtiam txo cov qog loj hlob. Cov ntaub ntawv no qhia tau hais tias muaj kev sib koom ua ke ntawm PNC-27 thiab paclitaxel, nrog PNC-27 tsom rau paclitaxel ntawm cell-surviving thiab txhim kho nws cov teebmeem antitumor.

5. Kev kho mob qog noj ntshav ntawm lub zes qe menyuam tseem ceeb

Ib txoj kev tshawb nrhiav tau tsim cov kab lis kev cai tshiab ntawm cov kab mob qog noj ntshav ntawm lub zes qe menyuam tshiab los ntawm cov neeg mob uas tau kuaj pom zes qe menyuam cystadenocarcinoma tshiab. Ib tug ntawm lawv yog los ntawm mucinous cystadenocarcinoma thiab lwm yam yog los ntawm qib papillary plasmacytoid carcinoma. Kev kho mob ntawm PNC-27 tau ntsuas ntau los ntawm kev soj ntsuam lub teeb pom kev zoo thiab MTT cell proliferation assay nrog rau kev ntsuas ntawm lactate dehydrogenase (LDH). Cov txiaj ntsig tau pom tias PNC-27 inhibited kev loj hlob ntawm tib neeg cov qog nqaij hlav qog noj ntshav tshiab tshiab cais tawm ntawm ob lub zes qe menyuam epithelial carcinomas nyob rau hauv koob tshuaj thiab yog cytotoxic rau lawv. Kev tswj peptide PNC-29 tsis muaj kev cuam tshuam rau thawj cov qog nqaij hlav cancer. Tsis tas li ntawd, PNC-27 kuj yog cytotoxic rau ntev-tsim thiab chemotherapy-resistant tib neeg zes qe menyuam kab mob qog noj ntshav ^[6].

Hauv cov ntsiab lus, PNC-27, raws li ib qho tshiab anticancer peptide, qhia tau hais tias muaj peev xwm tseem ceeb rau kev siv ntau yam kev kho mob qog noj ntshav. Hauv thaj tsam ntawm cov kab mob leukemia, PNC-27 tau nthuav tawm cov kev xaiv tua ntawm tus mob myeloid leukemia (piv txwv li, U937, OCI-AML3, thiab HL60 cell kab) thiab p53-tsis muaj K562 hlwb, thiab ua tiav cov nyhuv antitumor los ntawm inducing cell necrosis thiab lactate dehydrogenase tso tawm. Hauv kev kho mob qog noj ntshav ntawm zes qe menyuam, kev sib xyaw ntawm PNC-27 thiab paclitaxel tau pom muaj kev sib koom ua ke, uas tuaj yeem cuam tshuam cov qog loj hlob thiab tseem muaj kev tua cov tshuaj tiv thaiv kab mob. Tsis tas li ntawd, kev sib xyaw ntawm PNC-27 nrog liposomal tshuaj (xws li Doxil) raws li lub hom phiaj ligand tuaj yeem txhim kho qhov kev xa tawm tshwj xeeb thiab kev tiv thaiv qog noj ntshav ntawm cov tshuaj rau HDM2-zoo qog hlwb. Nws cov nyhuv inhibitory ntawm thawj epithelial zes qe menyuam qog noj ntshav progenitor hlwb ntxiv validates qhov chaw kho mob translational nqi. Tam sim no, PNC-27 tau nkag mus rau theem I kev sim tshuaj ntsuam xyuas, thiab xav tau kev tshawb fawb soj ntsuam ntau ntxiv txhawm rau txheeb xyuas nws txoj kev nyab xeeb thiab kev ua tau zoo mus ntev, txhawm rau txhawb nws ua ib qho kev daws teeb meem tshiab rau kev kho mob qog noj ntshav.

Hais Txog Tus Sau

Cov ntaub ntawv hais saum toj no yog txhua yam tshawb fawb, kho thiab sau los ntawm Cocer Peptides.

Scientific Journal Author

Sarafraz-Yazdi E yog tus kws tshawb fawb cuam tshuam nrog ntau lub koom haum, suav nrog NomoCan, New York Blood Center, SUNY Downstate Health Sciences University, thiab New York Harbor VA Med Ctr. Cov kev koom tes no qhia txog nws txoj kev koom tes hauv ntau yam kev tshawb fawb thiab kev kho mob ib puag ncig.

Nws cov kev tshawb fawb nyiam nthuav dav thoob plaws ntau yam kev kawm xws li Oncology, Kev Kho Mob Laboratory Technology, Pharmacology & Pharmacy, Biochemistry & Molecular Biology, thiab Kev Tshawb Fawb & Kev sim tshuaj. Nws txoj haujlwm hauv cov haujlwm no qhia txog nws txoj kev txawj ntse thiab kev mob siab rau kev nce qib kev paub hauv cov haujlwm tseem ceeb ntawm kev kho mob thiab kev tshawb fawb. yog teev nyob rau hauv cov ntaub ntawv ntawm kev hais lus [3].

▎ Cov Lus Qhia Tseem Ceeb

[1] Thadi A, Gleeson EM, Khalili M, et al. Anti-Cancer Tumor Cell Necrosis ntawm Epithelial Ovarian Cancer Cell Kab nyob ntawm qhov kev nthuav qhia siab ntawm HDM-2 Protein hauv lawv cov Membranes [J]. Annals of Clinical and Laboratory Science, 2020,50(5):611-624. https://pubmed.ncbi.nlm.nih.gov/33067207/

[2] Sookraj KA, Bowne WB, Adler V, et al. Cov tshuaj tiv thaiv kab mob qog noj ntshav, PNC-27, induces qog cell lysis raws li qhov tsis zoo peptide [J]. Cancer Chemotherapy and Pharmacology, 2010,66(2):325-331.DOI:10.1007/s00280-009-1166-7.

[3] Sarafraz-Yazdi E, Mumin S, Cheung D, et al. PNC-27, Chimeric p53-Penetratin Peptide khi rau HDM-2 nyob rau hauv p53 Peptide-zoo li Structure, Induces Selective Membrane-Pore Formation thiab ua rau Cancer Cell Lysis [J]. Biomedicines, 2022,10(5).DOI:10.3390/biomedicines10050945.

[4] Darban SA, Badiee A, Jaafari M R. PNC27 anticancer peptide raws li lub hom phiaj ligand txhim kho cov nyhuv antitumor ntawm Doxil hauv HDM2-expressing cells[J]. Nanomedicine, 2017, 12(12): 1475-1490.DOI: 10.2217/nnm-2017-0069.

[5] Alagkiozidis I, Gorelick C, Shah T, et al. Synergy ntawm Paclitaxel thiab Anti-Cancer Peptide PNC-27 hauv Kev Kho Mob Ovarian Cancer (Retraction of Vol 47, Pg 271, 2017)[J]. Annals of Clinical and Laboratory Science, 2017,47(4). https://pubmed.ncbi.nlm.nih.gov/28667027/

[6] Sarafraz-Yazdi E, Gorelick C, Wagreich AR, et al. Ex vivo Efficacy of Anti-Cancer Drug PNC-27 in the Treatment of Patient-Derived Epithelial Ovarian Cancer [J]. Annals of Clinical and Laboratory Science, 2015,45(6:650-658. https://pubmed.ncbi.nlm.nih.gov/26663795/

Tag nrho cov kab lus thiab cov ntaub ntawv ntawm cov khoom lag luam muab rau ntawm lub vev xaib no tsuas yog rau cov ntaub ntawv tshaj tawm kev tshaj tawm thiab cov hom phiaj kev kawm.  

Cov khoom muab rau hauv lub vev xaib no yog npaj tshwj xeeb rau kev tshawb fawb hauv vitro. Kev tshawb fawb hauv vitro (Latin: * hauv iav *, lub ntsiab lus hauv iav) yog ua los ntawm tib neeg lub cev. Cov khoom no tsis yog tshuaj, tsis tau txais kev pom zoo los ntawm US Food and Drug Administration (FDA), thiab yuav tsum tsis txhob siv los tiv thaiv, kho, lossis kho txhua yam mob, kab mob, lossis mob. Nws raug txwv nruj raws li txoj cai los qhia cov khoom no rau hauv tib neeg lossis tsiaj lub cev hauv txhua daim ntawv.