November 8, 2020/Medical College, Tibet University/Pharmaceutical Biology

Umbhalo/Wu Tingyao

Ingabe iziguli ezinomdlavuza zingayithathaI-Ganoderma lucidumngenkathi uthola ukwelashwa okuhlosiwe?Ngethemba ukuthi umbiko wocwaningo olandelayo unganikeza izimpendulo.

I-Gefitinib (GEF) ingeminye yemithi ebaluleke kakhulu okuhloswe ngayo ekwelapheni umdlavuza wamaphaphu osethuthukile kanye ne-metastatic non-small cell wamaphaphu (okuhlanganisa i-lung adenocarcinoma, umdlavuza wamaphaphu we-squamous cell, nomdlavuza wamaphaphu omkhulu wamangqamuzana), okuletha inhlansi yethemba ezigulini ezinesifo sikashukela. basinda ebumnyameni.Kodwa ukukhanya ekuphumeni komhubhe kungase kungahlali njalo, ngoba ukumelana nomuthi kuvame ukukhula ngemva kwezinyanga eziyishumi kuya kweziyishumi nesithupha zokwelashwa.

Ngakho-ke, uma singabamba isikhathi sokuthuthukisa umphumela wokwelapha we-GEF, zama ukwelapha umdlavuza wamaphaphu esimweni esilawuleka kangcono nesinakekelwa kangcono noma sinciphise imiphumela emibi yezidakamizwa ukuze iziguli zibe nesimo esingcono somzimba ukubhekana nazo. umdlavuza, mhlawumbe likhona ithuba lokwenza ukukhanya kwempilo kukhanye kakhudlwana.

Abacwaningi abavela eMnyangweni we-Oncology weSibhedlela Sezokwelapha SaseShayina saseYantai kanye neKolishi Lezokwelapha laseTibet University ngokuhlanganyela bashicilele umbiko wocwaningo "ku-Pharmaceutical Biology" ekupheleni kuka-2020 okufakazele ngokuhlolwa kwezilwane ukuthi i-adenocarcinoma yamaphaphu evame kakhulu endaweni engencane. umdlavuza wamaphaphu, ukusetshenziswa okuhlangene kweI-Ganodermalucidumi-triterpenoids (GLTs) kanye ne-GEF inganqanda ngempumelelo ukukhula kwesimila futhi yehlise imiphumela emibi yezidakamizwa, inikeze uhlelo olusha okufanele lucatshangelwe ngamasu okwelapha ahlobene.

Abacwaningi baqale bafaka imigqa yamaseli e-alveolar adenocarcinoma (imigqa yeseli ye-A549) ngaphansi kwesikhumba samagundane anamasosha omzimba asengozini.Ngemuva kokuthi ama-diameters ama-subcutaneous tumors angaba ngu-6-8 mm, aqala ukudlaI-Ganoderma lucidumi-triterpenoids (GLT, 1 g/kg/day), i-gefitinib (GEF, 15 mg/kg/ngosuku) noma inhlanganisela yakho kokubili izinsuku eziyi-14, futhi ukuhlola kwaphela ngosuku lwe-15.Kwavela ukuthi:

(1) Thuthukisa izinga lokuvimbela ukukhula kwesimila

Ama-GLT kanye ne-GEF angavimbela ukukhula kwamathumba e-adenocarcinoma yamaphaphu, kodwa inhlanganisela yakho kokubili inomphumela ongcono (Umfanekiso 1~3).

Umfanekiso 1 Izimila ezikhishwe emagundaneni e-adenocarcinoma yamaphaphu ekupheleni kokuhlolwa

Umfanekiso wesi-2 Izinguquko ekukhuleni kwesimila samagundane e-adenocarcinoma yamaphaphu ngesikhathi sokuhlolwa

Umfanekiso 3 Izinga lokuvimbela ukukhula kwesimila samagundane e-lung adenocarcinoma ngezindlela ezahlukene zokwelashwa

2) Qinisa ukuvinjwa kwe-angiogenesis yesimila kanye nokugqugquzelwa kwe-apoptosis yamangqamuzana omdlavuza

Amathumba adinga ukwakha imikhumbi emisha ukuze aqhubeke nokukhula.Ngakho-ke, ukuminyana kwama-microvessels ezicutshini zesimila sekuyisihluthulelo esibalulekile ekukhuleni okushelelayo kwamathumba.Umfanekiso 4 (A) ubonisa ukusatshalaliswa kwama-microvessel ezingcebeni zezicubu zesimila zeqembu ngalinye.Umfanekiso wesi-4 (B) ubonisa ukuthi inhlanganisela ye-GLT ne-GEF inomphumela ongcono wokuvinjelwa kunalokhu okubili kuphela.

Umfanekiso 4 Izingxenye zezicubu zesimila kanye nokuminyana kwe-microvessel yamagundane e-adenocarcinoma yamaphaphu

Ngamanye amazwi, inhlanganisela ye-GLTs ne-GEF ingavimba izicubu eziningi zesimila ekutholeni izakhamzimba futhi zenze izimila zibe nzima kakhulu ukukhula.Le nqubo yesenzo ivela ekulawuleni okuqinisiwe kokubonakaliswa kwezakhi zofuzo ezihlobene kanye nokukhishwa kwamaprotheni ezicubu ze-tumor, okuhlanganisa ukuvimbela "i-vascular endothelial growth factor receptor 2 (VEGFR2)" nokukhuthaza ukukhiqizwa kwe-"Angiostatin" kanye "ne-endostatin".

Ngaphezu kwalokho, abacwaningi baphinde baqaphela ezigabeni zezicubu ze-tumor zeqembu ngalinye lamagundane ukuthi ngaphansi kwesenzo esihlanganisiwe se-GLTs ne-GEF, ukugcinwa kweprotheyini (Bax) ekhuthaza i-apoptosis yamangqamuzana omdlavuza kuzokhula kakhulu ngenkathi ukugcinwa kwamaprotheni (Bcl- 2) evimbela i-apoptosis yamaseli omdlavuza izokwehla.Amangqamuzana e-adenocarcinoma yamaphaphu ayashesha ukukhula abheke lapho kuvela khona i-apoptosis kulokhu kuhlanganisa nokukhipha amandla.

(3) Yehlisa imiphumela emibi yezidakamizwa

Amagundane e-adenocarcinoma yamaphaphu alashwa kuphela nge-GEF ayenokuncipha kwesisindo esiningi kakhulu;ngakolunye uhlangothi, inhlanganisela ye-GLTs kanye ne-GEF ingagcina kangcono isisindo somzimba samagundane e-lung adenocarcinoma ── eseduze kakhulu naleyo yamagundane avamile (iqembu elivamile lokulawula) (Umfanekiso 5).

Ngaphezu kwalokho, amagundane e-adenocarcinoma yamaphaphu alashwa kuphela nge-GEF abonise ukukhathazeka, ukukhathala, ukozela, ukuncipha komsebenzi, ukunciphisa ukudla kanye nesikhumba esibuhlungu.Kodwa-ke, lezi zimo bezilula kakhulu noma zingabonakali eqenjini eliphathwe ngenhlanganisela ye-GLTs ne-GEF.Ngokusobala, ama-GLT angakwazi ukulungisa imiphumela emibi ebangelwa i-GEF.

Umfanekiso 5 Amajika amarekhodi esisindo kanye nezinguquko kumagundane e-adenocarcinoma yamaphaphu ngesikhathi sokuhlolwa

(4) Ukuphepha kwama-GLT

Ukuze kuhlolwe ukuphepha kwama-GLTs, abacwaningi benza imigqa evamile yamaseli e-alveolar epithelial cell BEAS-2B kanye nemigqa yeseli ye-alveolar adenocarcinoma A549 esetshenziswa ekuhlolweni kwezilwane ngokulandelana nama-GLTs in vitro amahora angama-48.

Imiphumela iboniswa ku-Figure 6. Lapho i-GLTs (i-concentrations ye-2.5 ne-5 mg / L) ivimbela izinga lokusinda kwamangqamuzana e-lung adenocarcinoma kuya ku-80-60%, amaseli avamile ayesaphila;ngisho nasekugxilweni okuphezulu, ama-GLT asaphatha ngokucacile amangqamuzana omdlavuza namaseli avamile ngendlela ehlukile, futhi lo mehluko ubaluleke nakakhulu kune-GEF (Umfanekiso 7).

Umfanekiso 6 Umphumela ovimbelayo wama-GLT ekukhuleni kwamaseli

Umfanekiso 7 Umthelela ovimbelayo we-gefitinib ekukhuleni kweseli

Ngokokuhlaziya komcwaningi, amanani e-IC50 e-GLTs ku-48 h wokwelashwa kwemigqa yeseli ye-A549 ayengu-14.38 ± 0.29 mg/L kuyilapho ama-GLT abonisa umphumela we-cytotoxic onamandla kancane kumugqa weseli we-BEAS-2B onenani le-IC50 lama-78.62 ± 2.53 mg/L, okusho ukuthi uma ama-GLT ebulala amangqamuzana omdlavuza, asengakwazi ukugcina izinga eliphezulu lokuphepha kumaseli avamile.

Ama-GLT nokwelashwa okuhlosiwe kuyahambisana, okwenza ukwelashwa kuthembise kakhulu.

Lo mbiko wocwaningo usibonisile:

Ngaphansi kwezimo zokuhlola ezifanayo, ukuphathwa ngomlomo kwe-GLTs kungase kungabi nomthelela ofanayo wokuvimbela kumathumba e-adenocarcinoma yamaphaphu omuntu njenge-GEF, kodwa ama-GLT awanayo imiphumela emibi ye-GEF.

Lapho ama-GLTs kanye ne-GEF esebenza ndawonye, ​​awakwazi nje ukukhulisa umphumela ovimbela ukukhula kwesimila kodwa futhi anciphise imiphumela ye-gefitinib esisindweni, emoyeni, emzimbeni, ekuthandeni ukudla nasesikhunjeni.Lokhu kubizwa ngokuthi "ukwandisa ukusebenza kahle kanye nokunciphisa ubuthi".

Isizathu esenza ukuthi ama-GLT athuthukise ukuvinjelwa kwe-GEF kwamathumba e-adenocarcinoma yamaphaphu sihlobene “nokuvimbela i-angiogenesis yesimila” kanye “nokukhuthaza i-apoptosis yamangqamuzana omdlavuza”.

Ukuze kuhlolwe umdlavuza womuntu ezilwaneni, abacwaningi basebenzisa amagundane anamasosha omzimba akhubazekile (ukuze amangqamuzana omdlavuza womuntu akhule ezinhlotsheni ezahlukene).Ngakho-ke, imiphumela ngokuyisisekelo yayiwumphumela we-GLTs kanye ne-GEF ngokwayo kumaseli omdlavuza.

Kodwa-ke, ekusetshenzisweni kwangempela kwe-anti-cancer, umsebenzi wamasosha omzimba kufanele uhileleke.Ngakho-ke, ngaphezu kwe-GLTs kanye ne-GEF, uma "ukungavikeleki okuhle" kwengezwa, ingabe imiphumela izobukeka kakhulu?

Abacwaningi abazange banikeze incazelo eningi yama-GLT asetshenziswe ekuhloleni, kodwa ngokusho kwencazelo yephepha, kufanele kube ukukhishwa okungahluziwe kwezinhlobonhlobo ze-GLT.Kodwa umthamo osebenzayo wegramu eyodwa ngekhilogremu yesisindo somzimba kumagundane empeleni muningi kakhulu.Lokhu kusitshela ukuthi izinhlelo zokusebenza zingadinga umthamo omkhulu ukuze zisebenze.Ngakolunye uhlangothi, futhi kusinika ithemba lokuthi esikhathini esizayo kungase kwenzeke ukuthola izithako ezibalulekile ezingasebenza kahle noma ezingcono ngemithamo ephansi.

Kunoma yikuphi, okungenani lolu cwaningo lubonise ukuthi ama-triterpenoids avela ku-Ganoderma lucidum awavimbi nje kuphela ukwelashwa kwezidakamizwa eziqondiswe emtholampilo ezivame ukusetshenziswa kodwa futhi abe nomthelela omuhle "wokwandisa ukusebenza kahle nokunciphisa ubuthi" ngokusekelwe ekuphepheni okukhulu.
Ukuphuthaza emhubheni omnyama kudinga ukukhanya kwekhandlela okwengeziwe ukuze kuhole indlela nokukhanyisa.Uma kuqhathaniswa nalawo “mathemba” angenakufinyeleleka noma okunzima ukuwakhiqiza ngobuningi, noma “izindlela zokupheka eziyimfihlo” ezinemithombo engaziwa nezithako,I-Ganoderma lucidumama-triterpenoids, angatholakala inqobo nje uma ufuna futhi uqongelele isipiliyoni sokusebenzisa isikhathi eside, kufanele kube okufanelekile ukuzama.

[Umthombo] Wei Liu, et al.I-Ganoderma triterpenoids inciphisa i-tumor angiogenesis kumdlavuza wamaphaphu amagundane anqunu aphethe isimila.I-Pharm Biol.2020: 58(1): 1061-1068.

PHELA

Mayelana nombhali/ Nks. Wu Tingyao
UWu Tingyao ubelokhu ebika ngolwazi lwe-Ganoderma lokuqala kusukela ngo-1999. Ungumbhali wencwadiUkwelapha nge-Ganoderma(ishicilelwe ku-People's Medical Publishing House ngo-Ephreli 2017).
 
★ Lesi sihloko sishicilelwe ngaphansi kokugunyazwa okukhethekile kombhali.★ Le misebenzi engenhla ayinakuphinda ikhiqizwe, ikhishwe noma isetshenziswe ngezinye izindlela ngaphandle kwemvume yombhali.★ Ngokuphulwa kwesitatimende esingenhla, umbhali uzolandela izibopho ezingokomthetho ezifanele.★ Umbhalo wokuqala walesi sihloko ubhalwe ngesiShayina nguWu Tingyao futhi wahunyushelwa esiNgisini ngu-Alfred Liu.Uma kukhona ukungqubuzana phakathi kokuhumusha (isiNgisi) kanye nokwangempela (isiShayina), isiShayina sangempela siyonqoba.Uma abafundi benemibuzo, sicela uthinte umbhali wokuqala, uNksz. Wu Tingyao.