{"id":7931,"date":"2024-08-11T09:50:54","date_gmt":"2024-08-11T09:50:54","guid":{"rendered":"https:\/\/longchangextracts.com\/?p=7931"},"modified":"2024-08-11T09:50:54","modified_gmt":"2024-08-11T09:50:54","slug":"guanggancao-ding","status":"publish","type":"post","link":"https:\/\/longchangextracts.com\/tr\/guanggancao-ding\/","title":{"rendered":"Guanggancao Ding'in kastrasyona diren\u00e7li prostat kanseri tedavisindeki etki mekanizmas\u0131n\u0131n a\u011f farmakolojisi ve deneysel do\u011frulamaya dayal\u0131 olarak ara\u015ft\u0131r\u0131lmas\u0131"},"content":{"rendered":"

Guanggancao Ding'in kastrasyona diren\u00e7li prostat kanseri tedavisindeki etki mekanizmas\u0131n\u0131n a\u011f farmakolojisi ve deneysel do\u011frulamaya dayal\u0131 olarak ara\u015ft\u0131r\u0131lmas\u0131
\nProstat kanseri (PCa), ya\u015fl\u0131 erkeklerin \u00fcreme sisteminde en s\u0131k g\u00f6r\u00fclen malign t\u00fcm\u00f6rd\u00fcr. Androjen yoksunlu\u011fu i\u00e7in bir\u00e7ok erken tedavi etkilidir, ancak \u00e7o\u011fu sonunda hormona duyarl\u0131 prostat kanserinden kastrasyona diren\u00e7li prostat kanserine (CRPC) ilerler. CRPC olduk\u00e7a \u00f6l\u00fcmc\u00fcl ve invaziv bir prostat kanseridir. CRPC hastalar\u0131n\u0131n 84%'sinden fazlas\u0131nda metastaz g\u00f6r\u00fcl\u00fcr ve ortalama sa\u011fkal\u0131m s\u00fcresi yaln\u0131zca 20 ayd\u0131r. Son y\u0131llarda yeni kemoterapi ila\u00e7lar\u0131 ve endokrin ila\u00e7lar ortaya \u00e7\u0131km\u0131\u015f olsa da, bu kemoterapi ila\u00e7lar\u0131n\u0131n bir\u00e7ok yan etkisi vard\u0131r ve endokrin ila\u00e7lar\u0131n ilac\u0131n etki s\u00fcresini k\u0131saltan diren\u00e7 sorunlar\u0131 vard\u0131r. Bu nedenle, kastrasyon direnci s\u00fcrecini geciktirmek ve CRPC'yi tedavi etmek i\u00e7in yeni ila\u00e7lar bulmak b\u00fcy\u00fck \u00f6nem ta\u015f\u0131maktad\u0131r.
\nGlabridin, meyan k\u00f6k\u00fcnden elde edilen, anti-enflamatuar, antioksidan, anti-t\u00fcm\u00f6r, n\u00f6roprotektif ve anti osteoporoz gibi \u00e7ok \u00e7e\u015fitli biyolojik aktivitelere sahip flavonoid bir bile\u015fiktir. Glisirizinin meme kanseri, karaci\u011fer kanseri, mide kanseri ve serviks kanserinde t\u00fcm\u00f6r h\u00fccresi proliferasyonunu inhibe etme ve apoptozu ind\u00fckleme konusunda iyi bir etkiye sahip oldu\u011fu bildirilmektedir. Bununla birlikte, glisirizinin CRPC \u00fczerindeki molek\u00fcler mekanizmas\u0131 tam olarak anla\u015f\u0131lamam\u0131\u015ft\u0131r. A\u011f farmakolojisi, farmakoloji, bilgisayar bilimi ve sistem biyolojisine dayal\u0131 bilgi a\u011flar\u0131n\u0131n bir kombinasyonudur ve karma\u015f\u0131k hastal\u0131klarda ila\u00e7 ke\u015ffi ve se\u00e7imi i\u00e7in yeni fikirler sa\u011flar. Guanggancao Ding'in CRPC \u00fczerindeki etki mekanizmas\u0131n\u0131 daha fazla ara\u015ft\u0131rmak i\u00e7in, a\u011f farmakolojisi, molek\u00fcler yerle\u015ftirme ve h\u00fccre deneylerini kullanarak etki mekanizmas\u0131n\u0131 ke\u015ffettik ve gelecekteki ila\u00e7 temel ara\u015ft\u0131rmalar\u0131 ve klinik uygulamalar\u0131 i\u00e7in referans sa\u011flad\u0131k.<\/p>\n

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\nSon y\u0131llarda prostat kanserinin geleneksel \u00c7in t\u0131bb\u0131 ile tedavisinde, \u00f6zellikle de CRPC'de \u00f6nemli ilerlemeler kaydedilmi\u015ftir. Geleneksel \u00c7in t\u0131bb\u0131n\u0131n cerrahi veya kemoterapi ile kombinasyonu, t\u00fcm\u00f6r boyutunu k\u00fc\u00e7\u00fcltme, PSA'y\u0131 d\u00fc\u015f\u00fcrme, n\u00fcks\u00fc azaltma ve hayatta kalma s\u00fcresini uzatma etkilerine sahiptir. Bir\u00e7ok ara\u015ft\u0131rma raporu meyan k\u00f6k\u00fcndeki aktif bile\u015fenlerin CRPC \u00fczerinde \u00f6nemli bir anti-t\u00fcm\u00f6r etkiye sahip oldu\u011funu g\u00f6stermektedir. Gioti ve arkada\u015flar\u0131 meyan k\u00f6k\u00fc ekstrakt\u0131n\u0131n (GGE) tek ba\u015f\u0131na veya doksorubisin ile kombinasyon halinde androjenden ba\u011f\u0131ms\u0131z prostat kanseri h\u00fccreleri (PC-3 h\u00fccreleri) \u00fczerinde anti proliferatif etkilere sahip oldu\u011funu ve LC3A, ULK1 ve AMBRA1 gibi otofaji ile ilgili genlerin ekspresyonunu te\u015fvik edebilece\u011fini bulmu\u015ftur. Zhang ve arkada\u015flar\u0131, isoliquiritigenin'in prostat kanseri h\u00fccrelerinin (PC-3 ve 22RV1) proliferasyonunu inhibe edebildi\u011fini, apoptozu ind\u00fckleyebildi\u011fini, G2\/M h\u00fccre d\u00f6ng\u00fcs\u00fcn\u00fc bloke edebildi\u011fini ve in vivo hayvan deneyleri yoluyla PC-3 ksenograftlar\u0131n\u0131n b\u00fcy\u00fcmesini inhibe edebildi\u011fini bulmu\u015flard\u0131r. Meyan k\u00f6k\u00fc m\u00fckemmel anti CRPC aktivitesi sergiler ve meyan k\u00f6k\u00fcndeki glisirizin, \u00e7ok dikkat \u00e7eken ve iyi anti-t\u00fcm\u00f6r aktivitesine sahip bir\u00e7ok flavonoidden biridir. CRPC'nin etki mekanizmas\u0131 daha fazla ara\u015ft\u0131r\u0131lmaya de\u011ferdir.
\nGeleneksel farmakoloji ile kar\u015f\u0131la\u015ft\u0131r\u0131ld\u0131\u011f\u0131nda, a\u011f farmakolojisi yeni ila\u00e7 geli\u015ftirme i\u00e7in yeni bir bak\u0131\u015f a\u00e7\u0131s\u0131 sa\u011flar. Glisirizinin CRPC \u00fczerindeki etki mekanizmas\u0131n\u0131 daha iyi anlamak i\u00e7in, TCMIO, TCMSP ve PharmMapper gibi veritabanlar\u0131 arac\u0131l\u0131\u011f\u0131yla glisirizinin 683 hedefini toplamak i\u00e7in a\u011f farmakolojisi y\u00f6ntemlerini kulland\u0131k. Venn diyagram\u0131 ara\u00e7lar\u0131n\u0131 kullanarak kastrasyona diren\u00e7li prostat kanseri i\u00e7in glisirizinin 55 anahtar hedefini elde ettik ve PPI protein etkile\u015fim a\u011f\u0131 analizi yoluyla AKT1, TP53, ESR1, EGFR ve ALB gibi 10 \u00e7ekirdek hedefi belirledik. GO zenginle\u015ftirme analizi glisirizinin esas olarak protein fosforilasyonunu, oksidasyon reaksiyonlar\u0131n\u0131 ve h\u00fccre d\u00f6ng\u00fcs\u00fcn\u00fc d\u00fczenleyerek h\u00fccre metabolizmas\u0131n\u0131 ve apoptozu d\u00fczenledi\u011fini g\u00f6stermi\u015ftir. Molek\u00fcler yerle\u015ftirme ayr\u0131ca glisirizinin 10 \u00e7ekirdek hedef ile iyi bir yerle\u015ftirme aktivitesine sahip oldu\u011funu g\u00f6stermi\u015ftir. Glisirizinin bu \u00e7ekirdek hedef proteinlerin ekspresyonunu d\u00fczenleyerek anti-t\u00fcm\u00f6r etkiler elde edebilece\u011fi \u00f6ng\u00f6r\u00fclmektedir. Bu \u00e7ekirdek hedefler aras\u0131nda AKT1 proteini en y\u00fcksek kenetlenme aktivitesine sahiptir. AKT1, t\u00fcm\u00f6rlerin \u00e7e\u015fitli biyolojik s\u00fcre\u00e7lerinde yer alan PI3K\/AKT sinyal yolundaki \u00f6nemli d\u00fczenleyici fakt\u00f6rlerden biridir. Prostat kanserinde, genom ve transkriptom profillerine dayal\u0131 olarak primer prostat kanserinin 42%'sinde ve metastatik prostat kanseri \u00f6rneklerinin 100%'sinde PI3K\/AKT yola\u011f\u0131 bile\u015fenlerinin genetik varyasyonlar\u0131 ve gen ekspresyonu d\u00fczensizli\u011fi tespit edilmi\u015ftir. \u0130lk \u00e7al\u0131\u015fmalarda, AKT alt tiplerinin (AKT1, AKT2) prostat kanserinde androjene duyarl\u0131 evreden hormona refrakter evreye ge\u00e7i\u015fi te\u015fvik edebilece\u011fi \u00f6ne s\u00fcr\u00fclm\u00fc\u015ft\u00fcr. CRPC hastalar\u0131n\u0131n tedavisine ili\u015fkin temel ara\u015ft\u0131rmalar temelinde, \u00e7al\u0131\u015fmalar kastrasyona diren\u00e7li prostat kanseri hayvan modellerinde AKT1\/2'nin nakavt edilmesinin in vivo ve in vitro metastazlar\u0131 \u00f6nemli \u00f6l\u00e7\u00fcde azaltt\u0131\u011f\u0131n\u0131 bildirmi\u015ftir. AKT1 ekspresyonunun inhibe edilmesinin CRPC hastalar\u0131n\u0131n sa\u011fkal\u0131m prognozunu iyile\u015ftirebilece\u011fi ve AKT1 inhibit\u00f6rlerinin CRPC hastalar\u0131 i\u00e7in potansiyel bir tedavi olabilece\u011fi g\u00f6r\u00fclebilir. \u00c7al\u0131\u015fmam\u0131z teorik olarak glisirizinin bir AKT1 inhibit\u00f6r\u00fc olabilece\u011fini d\u00fc\u015f\u00fcnd\u00fcrmektedir, ancak glisirizinin CRPC hastalar\u0131 i\u00e7in etkili bir AKT1 inhibit\u00f6r\u00fc olup olamayaca\u011f\u0131n\u0131n gelecekte daha fazla deneysel do\u011frulamaya ihtiyac\u0131 vard\u0131r.
\nKEGG yola\u011f\u0131 zenginle\u015ftirme sonu\u00e7lar\u0131 PI3K\/AKT sinyal yola\u011f\u0131 ve proteoglikanlar\u0131n kanser, prostat kanseri, kemokin resept\u00f6r aktivasyonu, endokrin direnci ve epidermal b\u00fcy\u00fcme fakt\u00f6r\u00fc resept\u00f6r tirozin kinaz inhibit\u00f6rlerine diren\u00e7 dahil 105 ilgili sinyal yola\u011f\u0131nda yer ald\u0131\u011f\u0131n\u0131 g\u00f6stermi\u015ftir (P<0.01). Bunlar aras\u0131nda, en endi\u015fe verici olan\u0131 fosfatidil-3-kinaz (PI3K)\/serin treonin protein kinaz (AKT) sinyal yola\u011f\u0131d\u0131r. PI3K\/AKT sinyal yolu h\u00fccresel metabolizman\u0131n, b\u00fcy\u00fcmenin, \u00e7o\u011falman\u0131n, farkl\u0131la\u015fman\u0131n ve protein sentezinin d\u00fczenlenmesinde rol oynar. PI3K\/AKT sinyal yola\u011f\u0131ndaki mutasyonlar bir\u00e7ok insan t\u00fcm\u00f6r\u00fcnde tespit edilmi\u015ftir. Ara\u015ft\u0131rma verileri, ilerlemi\u015f prostat kanseri hastalar\u0131n\u0131n 70% ila 100% kadar\u0131n\u0131n PI3K yola\u011f\u0131nda d\u00fczensizlik ya\u015fad\u0131\u011f\u0131n\u0131 g\u00f6stermektedir. Ve PI3K\/AKT sinyal yolunun hormona duyarl\u0131 prostat kanserinin kastrasyona diren\u00e7li prostat kanserine ilerlemesinde \u00f6nemli bir rol oynad\u0131\u011f\u0131 ve etki mekanizmas\u0131n\u0131n CRPC i\u00e7in potansiyel bir biyobelirte\u00e7 olarak hizmet edebilecek androjen resept\u00f6r\u00fc (AR) sinyal yolunun d\u00fczenlenmesiyle ilgili olabilece\u011fi bulunmu\u015ftur. \u015eu anda, AZD5363 gibi PI3K\/AKT sinyal yola\u011f\u0131 ile ilgili inhibit\u00f6rler klinik deneme a\u015famas\u0131na girmi\u015f ve \u00f6nemli terap\u00f6tik etkiler elde etmi\u015ftir. Bu yolakla ilgili inhibit\u00f6rlerin incelenmesi, CRPC tedavisinde \u00f6nemli bir de\u011fere sahiptir.
\nAyr\u0131ca CCK8 y\u00f6ntemi ile glisirizinin PC-3 h\u00fccrelerinin proliferasyonunu \u00f6nemli \u00f6l\u00e7\u00fcde inhibe edebildi\u011fini bulduk. Ak\u0131\u015f sitometrisi ve DAPI boyama deneyleri h\u00fccre apoptozunu ind\u00fckleyebildi\u011fini g\u00f6sterdi ve mikroskop alt\u0131nda h\u00fccre say\u0131s\u0131nda azalma ve morfolojik k\u00fc\u00e7\u00fclme g\u00f6zlendi. Anti-t\u00fcm\u00f6r ila\u00e7 konsantrasyonlar\u0131n\u0131n taranmas\u0131 i\u00e7in, IC50'lerinin biraz daha y\u00fcksek oldu\u011funu bulduk, bu da molek\u00fcler yerle\u015ftirme i\u00e7in kullan\u0131lan yar\u0131 esnek yerle\u015ftirme y\u00f6ntemiyle ilgilidir. Esnek kenetlenme ile kar\u015f\u0131la\u015ft\u0131r\u0131ld\u0131\u011f\u0131nda, yar\u0131 esnek kenetlenme ile hesaplanan ba\u011flanma enerjisi daha d\u00fc\u015f\u00fckt\u00fcr. Ayr\u0131ca, do\u011fal bir antioksidan olarak glisirizin g\u00fc\u00e7l\u00fc antioksidan etkilere sahiptir. Bununla birlikte, d\u00fc\u015f\u00fck doz do\u011fal antioksidanlar anti-t\u00fcm\u00f6r deneylerinde iyi anti-t\u00fcm\u00f6r aktivitesi g\u00f6stermezken, y\u00fcksek doz do\u011fal antioksidanlar h\u00fccreler \u00fczerinde toksik etkilere sahiptir ve spesifik mekanizmas\u0131n\u0131n daha fazla ara\u015ft\u0131r\u0131lmas\u0131 gerekir. A\u011f farmakolojisi taraf\u0131ndan tahmin edilen KEGG sinyal yoluna dayanarak, glisirizinin PC-3 h\u00fccreleri \u00fczerindeki inhibit\u00f6r etkisinin esas olarak PI3K\/AKT sinyal yolu ile ili\u015fkili olabilece\u011fini tahmin ediyoruz. Glisirizinin PC-3 h\u00fccrelerinde PI3K\/AKT sinyal yola\u011f\u0131 ile ilgili proteinlerin ekspresyonu \u00fczerindeki etkisini ara\u015ft\u0131rmak i\u00e7in Western blot deneyleri yap\u0131lm\u0131\u015ft\u0131r. Sonu\u00e7lar, glisirizinin AKT proteinlerinin fosforilasyon s\u00fcrecini \u00f6nemli \u00f6l\u00e7\u00fcde inhibe edebildi\u011fini g\u00f6sterdi. Deneyimizde, glisirizinin fosforlanm\u0131\u015f AKT proteininin ekspresyonunu \u00f6nemli \u00f6l\u00e7\u00fcde inhibe edebildi\u011fi, ancak fosforlanm\u0131\u015f PI3K proteininin ekspresyonu \u00fczerindeki inhibit\u00f6r etkinin beklendi\u011fi gibi olmad\u0131\u011f\u0131 g\u00f6zlenmi\u015ftir. Protein y\u00fckleme konsantrasyonunu ve oran\u0131n\u0131 tekrar tekrar ayarlad\u0131ktan ve i\u015flemi s\u0131k\u0131 bir \u015fekilde standardize ettikten sonra, protein hala \u00f6nemli etkiler g\u00f6stermedi. Bunun nedeninin, d\u00fc\u015f\u00fck potansiyele sahip olan p-PI3K proteininin kalite sorunu ile ilgili olabilece\u011fi d\u00fc\u015f\u00fcn\u00fclmektedir. Bununla birlikte, bu \u00e7al\u0131\u015fma i\u00e7in s\u0131n\u0131rl\u0131 finansman nedeniyle, di\u011fer \u00fcr\u00fcnlerin proteinlerini de\u011fi\u015ftirmedik. Gelecekteki deneylerde, hipotezimizi do\u011frulamak i\u00e7in bu yolakla ilgili daha fazla proteini analiz edece\u011fiz.
\n\u00d6zetle, bu \u00e7al\u0131\u015fma glisirizinin kastrasyona diren\u00e7li prostat kanseri \u00fczerindeki potansiyel etki mekanizmas\u0131n\u0131 a\u011f farmakolojisi yoluyla analiz ve tahmin etmi\u015f ve ayr\u0131ca molek\u00fcler yerle\u015ftirme ve in vitro h\u00fccre deneyleri yoluyla do\u011frulam\u0131\u015ft\u0131r. Sonu\u00e7lar, glisirizinin PC-3 h\u00fccrelerinin proliferasyonunu inhibe edebildi\u011fini ve apoptozu ind\u00fckleyebildi\u011fini ve mekanizmas\u0131n\u0131n AKT proteininin fosforilasyon s\u00fcreci ile ili\u015fkili oldu\u011funu g\u00f6stermi\u015ftir. Bu nedenle, anti CRPC mekanizmas\u0131n\u0131n esas olarak PI3K\/AKT sinyal yola\u011f\u0131 ile ilgili proteinlerin fosforilasyonunu d\u00fczenleyerek olabilece\u011fini tahmin ediyoruz. Bu \u00e7al\u0131\u015fma sadece Guanggancao Ding'in kastrasyona diren\u00e7li prostat kanseri tedavisindeki molek\u00fcler mekanizmas\u0131n\u0131 ke\u015ffetmek i\u00e7in ara\u015ft\u0131rma fikirleri sa\u011flamakla kalmamakta, ayn\u0131 zamanda meyan k\u00f6k\u00fcndeki flavonoidleri i\u00e7eren anti-t\u00fcm\u00f6r ila\u00e7lar\u0131n geli\u015ftirilmesi ve klinik uygulamas\u0131 i\u00e7in etkili bir y\u00f6ntem sunmaktad\u0131r.<\/p>","protected":false},"excerpt":{"rendered":"

Exploring the mechanism of action of Guanggancao Ding in treating castration resistant prostate cancer based on network pharmacology and experimental verification Prostate cancer (PCa) is the most common malignant tumor in the reproductive system of elderly men. Many early treatments for androgen deprivation are effective, but most eventually progress from hormone sensitive prostate cancer to […]<\/p>","protected":false},"author":1,"featured_media":0,"comment_status":"closed","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[20],"tags":[],"yoast_head":"\nExploring the mechanism of action of Guanggancao Ding in treating castration resistant prostate cancer based on network pharmacology and experimental verification - China Chemical Manufacturer<\/title>\n<meta name=\"robots\" content=\"index, follow, max-snippet:-1, max-image-preview:large, max-video-preview:-1\" \/>\n<link rel=\"canonical\" href=\"https:\/\/longchangextracts.com\/tr\/guanggancao-ding\/\" \/>\n<meta property=\"og:locale\" content=\"tr_TR\" \/>\n<meta property=\"og:type\" content=\"article\" \/>\n<meta property=\"og:title\" content=\"Exploring the mechanism of action of Guanggancao Ding in treating castration resistant prostate cancer based on network pharmacology and experimental verification - China Chemical Manufacturer\" \/>\n<meta property=\"og:description\" content=\"Exploring the mechanism of action of Guanggancao Ding in treating castration resistant prostate cancer based on network pharmacology and experimental verification Prostate cancer (PCa) is the most common malignant tumor in the reproductive system of elderly men. 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