TWI414307B - 小孢子靈芝免疫調節蛋白 (gmi)之新用途 - Google Patents
小孢子靈芝免疫調節蛋白 (gmi)之新用途 Download PDFInfo
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- TWI414307B TWI414307B TW099142868A TW99142868A TWI414307B TW I414307 B TWI414307 B TW I414307B TW 099142868 A TW099142868 A TW 099142868A TW 99142868 A TW99142868 A TW 99142868A TW I414307 B TWI414307 B TW I414307B
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Description
本發明係關於小孢子靈芝免疫調節蛋白(GMI)之新用途、GMI和抗癌劑之組合治療以及包含GMI和抗癌劑之醫藥組成物。特言之，GMI可用於抑制EGF受體活性，治療癌細胞侵襲和轉移以及促進傷口癒合。
新血管生成為腫瘤的生長之關鍵且對於各種血管新生的疾病很重要，例如糖尿病視網膜病變、關節炎、乾癬及血管瘤。70%以上的癌症病患死於初腫瘤之轉移散播。腫瘤新血管生成作用為原發腫瘤存活及轉移散播之關鍵性過程。血管生成性類固醇及帶有抗血管生成劑例如魚精蛋白(protamin)之肝素已用作抑制腫瘤生長之治療。這些方法有重大的限制，因為當肝素的劑量超過抑制血管新生之最適量時，會刺激腫瘤生長和血管新生。又，抗血管新生所需之高劑量的可體松(cortisone)會導致免疫抑制。獲得血管新生表型已然成為增生過渡至腫瘤之標記。
生長因子為引發細胞增生之物質，典型地係藉由與細胞表面之專一性受體結合來進行。一種此類的生長因子為表皮生長因子(EGF)。EGF引發活體內各種細胞的增生，且為大多數培養細胞之生長所需。EGF為具有6 Kd分子量(53個胺基酸殘基)及三個內雙硫鍵之單鏈多肽。這三個特性完整之表皮生長因子肽的內雙硫鍵係定義為「環(loop)」，A、B和C環。一般而言，A環的特性為介於1-19個胺基酸殘基，B環的特性為介於20-31個胺基酸殘基，及C環的特性為介於34-43個胺基酸殘基。EGF已知亦為一強力的細胞增生刺激物。特言之，EGF在各種製備物中已顯現可刺激上皮細胞組織之生長。上皮生長因子受體(EGFR)在上皮生物學上及許多人類的惡性腫瘤上扮演重要的角色。EGFR係與病毒致癌基因v-erb B有關，並過度表現在許多人類的腫瘤上，包括腦癌、膀胱癌、乳癌及頭，頸和肺之麟狀細胞癌。因此，EGF-R「活化」為刺激許多正常細胞分化以及某些腫瘤細胞異常生長之重要調節現象。完整的EGF胜肽及模仿其作用之抗體已用於各種方法中，如篩選抗腫瘤活性及促進傷口癒合。EGFR為受體家族之一成員，其包括四個高同源性蛋白，HER2、HER3和HER4以及EGFR。在此家族中這些蛋白係由一胞外區、一跨膜區及一胞內酪胺酸激酶區所組成。結合配體，如上皮生長因子(EGF)會活化胞內酪胺酸激酶區而引發受體之自磷酸化，此舉啟動涉及細胞增生和存活之訊號傳遞集聯。EGFR為癌症治療中最適合的標的之一。
肺癌為男性和女性中最常見的惡性腫瘤，且仍為癌症相關死因之首位。非小細胞肺癌佔有肺癌之約75-85%。傳統的肺癌治療一般臨床反應差，因此開發針對癌症轉移之新穎的治療方法極為重要。EGFR過度表現發生在40-80%之非小細胞肺癌(NSCLC)中。EGFR途徑造成人類癌症之發病及惡化，其包括細胞增生、凋亡、血管新生及轉移傳播。值得注意的，EGFR-導向的酪胺酸激酶抑制劑(TKI)例如吉非替尼(gefitinib)(艾瑞沙(Iressa),ZD1839)、拉帕替尼(lapatinib)(泰嘉(Tykerb),GW572016)及厄洛替尼(erlotinib)(得舒緩(Tarceva),OSI-774)，依NSCLC病患之特定的亞型，係具有不同的敏感性。此外，吉非替尼已用於NSCLC，為中等效力之單一藥劑。然而，病患對此藥劑的反應不同，且最近這些反應係與EGFR之酪胺酸激酶區中活化突變之存在有關。EGF與EGFR的相互作用，使得受體二聚化，活化其激酶活性並使酪胺酸殘基上的EGFR自磷酸化。EGF經由不同的途徑，亦與各種惡性腫瘤之生長和侵襲有關。數個研究已顯示EGF在肺癌中常會升高，且EGF之上調作用已顯示係與疾病惡化和預後差有關(Gorgoulis等人,1992,Anticancer Res,12,1183-1187)。此研究顯示EGF在肺腫瘤發生上扮演主要的角色。因此，EGF/EGFR的相互作用對癌症發展可能很重要。
植物藥治療已逐漸被視為可行的癌症之替代治療。靈芝(一種擔子菌)為一種草藥菇類，用作傳統的中藥已至少2,000年。許多靈芝類之治療效用已有記載，例如免疫調節、抗腫瘤、保肝、抗氧化及降膽醇效用(Jinn等人,2006,Biosci Biotechnol Biochem
,70,2627-2634)。所有的這些治療效用係歸因於三萜類、多醣體及糖蛋白(Boh等人,2007,Biotechnol Annu Rev
,13,265-301；Jinn等人,2006,Biosci Biotechnol Biochem
,70,2627-2634)。最近已辨識出一種稱為真菌免疫調節蛋白(FIP)之新的靈芝糖蛋白。到目前，至少已有四種FIP已由赤芝(G
.lucidum
)LZ-8中分離出並純化，其包括FIP-fve(金針菇Flammulina veltipes
)、FIP-vvo(草菇Volvariella volvacea
)、FIP-gts(松杉靈芝Ganoderma tsugae
)及FIP-gja(紫芝Ganoderma sinensis
)(Hsu等人,1997,Biochem J
,323(Pt 2),557-565；Ko等人,1995,Eur J Biochem
,228,244-249；Xuanwei等人,2008,Planta Med
,74,197-200)。根據先前的研究，松杉靈芝(一種亞洲普遍的化學預防性菇類)之FIP-gts，具有抗癌功能並與hTERT/端粒酶表現之調節有關(Liao等人,2006,Mol Carcinog
,45,220-229)。此外，FIP-gts抑制A549癌細胞生長，造成細胞週期中止，因而引發肺癌細胞提早老化。再者，在植入A549細胞的無胸腺裸小鼠中，FIP-gts對腫瘤生長產生顯著的抑制作用(Liao等人,2008,Food Chem Toxicol
,46,1851-1859)。US 20100009915提供了一種抑制癌細胞增生之方法及抑制癌細胞移動之方法，其包括給予癌細胞經純化的真菌免疫調節蛋白LZ-8之多肽。
US 7,601,808揭示了一種由小孢子靈芝選殖出的免疫調節蛋白(GMI)，且該蛋白具有免疫調節劑之功效。然而，因GMI為一種新發現的免疫調節蛋白且其抗癌功效尚未探究出，因此在本項技術中仍需就其抗癌應用進行研究。
本發明之一目的係提供抑制EGF受體活性之方法，其包括將EGF受體與小孢子靈芝免疫調節蛋白(GMI)或其重組物接觸。
本發明之另一目的係提供治療癌細胞侵襲和轉移之方法，其包括投予一有效量之小孢子靈芝免疫調節蛋白(GMI)或其重組物至需要此項治療之個體中。
本發明另一目的係提供包括GMI或其重組物及抗癌劑之醫藥組成物。
本發明係基於發現小孢子靈芝免疫調節蛋白(GMI)可有效抑制EGF受體活性及治療癌細胞之侵襲和轉移。特言之，GMI經由阻斷EGF/phosphoEGFR-PI3K/Akt路徑抑制EGF-引發的癌細胞侵襲性生長(包括遷移和侵襲)。隨著GMI濃度增加，GMI引起劑量依賴之侵襲降低。本發明亦發現在GMI壓抑EGF-引發的EGF/phosphoEGFR-PI3K/Akt路徑之活化後，肌動蛋白顯著改變，所以GMI可用作腫瘤細胞之強力的肌動蛋白解聚劑。這些發現顯示GMI具有相當的癌症化學預防潛力。特言之，GMI與抗癌藥組合對治療及/或預防癌症或抑制轉移或侵襲提供了有利的效應(較佳地增效效應)。
在一方面，本發明係提供抑制EGF受體活性之方法，其包括將EGF受體與小孢子靈芝免疫調節蛋白(GMI)或其重組物接觸。
在另一方面，本發明係提供治療癌症侵襲和轉移之方法，其包括投予一有效量之小孢子靈芝免疫調節蛋白(GMI)或其重組物至需要此項治療之個體中。在一實施例中，係經由阻斷EGF/phosphoEGFR-PI3K/Akt路徑來治療侵襲和轉移。
在另一方面，本發明係提供抑制及/或治療癌症及/或癌症侵襲和轉移之方法，其包括同時、連續或分開投予GMI或其重組物及抗癌藥。在另一方面，本發明係提供包含GMI或其重組物及抗癌藥之醫藥組成物。
在另一方面，本發明係提供包含GMI或其重組物及抗癌藥之醫藥組成物。較佳地，該組成物對於治療及/或預防癌症具有增效效應。
根據本發明，免疫調節蛋白(GMI)係來自小孢子靈芝或其重組物。更佳地，該GMI具有下列之胺基酸序列：(1)-Leu-Ala-Trp-Asn-Val-Lys-(LAWNVK；SEQ ID NO:1)及(2)-Asp-Leu-Gly-Val-Arg-Pro-Ser-Tyr-Ala-Val-(DLGVRPSYAV；SEQ ID NO:2)，或下列之胺基酸序列：MSDTALIFTLAWNVKQLAFDYTPNWGRGRPSSFIDTVTFPTVLTDKAYTYRVVVSGKDLGVRPSYAVESDGSQKINFLEYNSGYGIADTNTIQVYVIDPDTGNNFIVAQWN(SEQ ID NO:3)。
根據本發明，術語「治療」及其類似語詞，用於本文中一般係指得到所欲的藥理、生理或美粧效用。該效用就完全或部分預防症狀、外觀、疾病或癥狀而言可為預防性的，及/或就部分或完全治癒症狀及/或因症狀或疾病所造成的不良效應而言可為治療性的。如文中所用之「治療」係涵蓋哺乳動物，特別是人類的任何症狀、疾病或不欲的外觀之治療，且其包括：(a)於一對象中預防疾病(例如癌症)、症狀(疼痛)或外觀(例如可視性腫瘤)免於發生，其中該對象可能易罹患該病症但尚未觀察到或診斷出患有該病症；(b)抑制疾病(例如癌症)、症狀(疼痛)或外觀，亦即使疾病(例如癌症)、症狀(疼痛)或外觀回復；(c)舒緩疾病(例如癌症)、症狀(疼痛)或外觀，亦即使症狀(疼痛)或外觀回復。
如文中所用與癌症侵襲轉移有關之術語「抑制」係指任何藉由本發明之GMI或醫藥組成物減少癌症侵襲和轉移。
術語「有效量」為當該化合物投予一對象時達到有利的臨床結果之化合物量。例如，當本發明化合物投予一患有癌症之對象時，「有利的臨床結果」包括腫瘤瘤體減小、轉移減低、與該癌症有關的癥狀之嚴重度減低及/或該對象之壽命增加。
根據本發明，術語「轉移」或「侵襲」係指細胞穿過生理屏障遷移或遷移到胞外基質之蛋白酶組份的能力。較佳的生理屏障包括本項技術熟知的基底膜或其他的胞外基質。細胞侵襲係與細胞蛋白質分解酵素之分泌或排泄有關。較佳的蛋白質分解酵素包括MMP。
在一實施例中，癌細胞之侵襲和轉移為表皮生長因子媒介之癌細胞遷移和侵襲。表皮生長因子(EGF)為與TGF-α分子之區域具同源性之小分子。其係由巨噬細胞和表皮細胞以角質細胞和纖維母細胞為目標所產生。其主要的角色係刺激角質細胞移行越過受傷的過渡性基質並引發表皮再生。EGF，如同所有的生長因子，係與回應細胞之表面上專一高親和力、小容量受體結合。EGF受體本質上具酪胺酸激酶活性，其因與EGF結合而活化。EGF受體之激酶區以訊號傳導集聯磷酸化EGF受體本身(自磷酸化作用)以及其他蛋白，其係與受體隨後的活化有關。EGFR之活化高度地涉入腫瘤增生和惡化之過程，包括細胞增生、抑制凋亡、血管新生和轉移。在上皮癌症中EGFR顯現相當高量的表現，且此表現係與腫瘤惡化相關，因此其為癌症治療中最適合的標的之一。
較佳地，該癌症為肺癌(更佳地，非小細胞肺癌，NSCLC)、肺，頭和頸之鱗狀細胞癌、乳癌、卵巢癌、前列腺癌、胃癌、子宮頸癌、食道癌、膀胱癌、腦癌、肝癌或大腸癌。
在另一實施例中，作為促進傷口癒合之治療劑，GMI可以局部治療的形式用於外部塗敷在任何受損的皮膚症狀。就此項應用，係希望GMI以偶聯的形式包括一載劑。例如，受損的皮膚症狀包括外部皮膚損傷例如燒傷、疹子、擦傷及其類似症狀。GMI作為治療促進傷口癒合之用途預期特別適合治療燒傷。
GMI可單獨或將其與適合的載劑和賦形劑混合成醫藥組成物投予病患。GMI可以非經腸給藥，例如以靜脈注射或輸液、腹膜內注射、皮下注射或肌肉內注射。GMI可經由與載劑和賦形劑形成錠劑、片劑、膠囊、液體、凝膠、糖漿、漿液、懸浮亦及其類似物等適當的調配物，以口服或直腸給藥。GMI可局部給藥，例如以皮膚貼片。GMI可調配成適合局部施用於皮膚或黏膜表面之乳膏、皮膚或黏膜貼片、液體或凝膠。GMI可以吸入器投藥至呼吸道中供局部或全身性治療癌症。在一實施例中，就60公斤的人類，所投予的GMI量之範圍可從250 μg至500 μg。
適合用於本發明之GMI劑量可由熟習本項技術者依照本文之揭示來決定。該藥品將含有一有效劑量的GMI(依照給藥路徑和活性藥劑之藥物動力學而定)及適合特定調配物給藥路劑(亦即，口服、非經腸、局部或吸入)之適合的醫藥載劑和賦形劑。GMI係藉由混合、溶解、造粒、製成糖衣錠、乳化、包膠、包埋或凍乾程序混合成醫藥調配物。供非經腸給藥之醫藥調配物包括水溶性形式之本發明多肽的水溶液。此外，本發明多肽之懸浮液可製備成油質注射懸浮液。適合的親脂性溶劑或媒劑包括油脂例如芝麻油，或合成的脂肪酸酯例如油酸乙酯或三酸甘油酯或脂質體。水性的注射懸浮液可含有增加懸浮液黏度之物質例如羧甲基纖維素鈉、山梨糖醇或葡聚糖。懸浮液可視需要含有安定劑或增加複合物或組合物溶解度，使溶液濃度更高之試劑。
在一實施例中，GMI可與放射治療和化療組合使用。
在另一實施例中，GMI或其重組物可與抗癌劑組合供癌症及/或癌症侵襲和轉移之組合治療。GMI或其重組物亦可與抗癌劑組合成醫藥組成物。亦即，本發明係提供包含GMI或其重組物及抗癌劑之醫藥組成物，且該組成物可治療及/或預防癌症，或治療及/或預防癌症轉移和侵襲。較佳地，該癌症為肺癌(更佳地，非小細胞肺癌,NSCLC)、肺，頭和頸之鱗狀細胞癌、乳癌、卵巢癌、前列腺癌、胃癌、子宮頸癌、食道癌、膀胱癌、腦癌、肝癌或大腸癌。特言之，該組成物較佳地係具有增效效力。根據本發明，抗癌劑包括(但不限於)：20-epi-1,25二羥基維生素D3；5-乙炔基尿嘧啶；阿比特龍(abiraterone)；阿柔比星(aclarubicin)；醯基富烯(acylfulvene)；腺環戊醇(adecypenol)；阿多來新(adozelesin)；阿地白介素(aldesleukin)；ALL-TK拮抗劑；六甲蜜胺(altretamine)；胺莫司汀(ambamustine)；2,4-二氯苯氧乙酸(amidox)；胺磷汀(amifostine)；胺基酮戊酸(aminolevulinic acid)；諳柔比星(amrubicin)；安吖啶(amsacrine)；阿那格雷(anagrelide)；阿那曲唑(anastrozole)；穿心蓮內酯(andrographolide)；血管新生抑制劑；拮抗劑D；拮抗劑G；安雷利克斯(antarelix)；抗背部化形態發生蛋白-1；抗雄激素，前列腺癌；抗雌激素；抗瘤酮(antineoplaston)；反義寡核苷酸；阿非迪黴素甘胺酸鹽(phidicolin glycinate)；凋亡基因調節劑；凋亡調節因子；脫嘌呤核酸；ara-CDP-DL-PTBA；精氨酸去胺酶；阿蘇吖啶(asulacrine)；阿他美坦(atamestane)；阿莫司汀(atrimustine)；阿西他汀(axinastatin 1；阿西他汀2(axinastatin 2)；阿西他汀3(axinastatin 3)；阿扎司瓊(azasetron)；阿扎毒素(azatoxin)；重氮酪胺酸；漿果赤黴素(baccatin) III衍生物；(baianol)；巴馬司他(batimastat)；BCR/ABL拮抗劑；苯并二氫卟吩(benzochlorins)；苯甲醯基星孢菌素(benzoylstaurosporine)；β內醯胺衍生物；(β-alethine)；β克林達黴素(betaclamycin B)；樺木酸(betulinic acid)；bFGF抑制劑；比卡魯胺(bicalutamide)；比生群(bisantrene)；雙氮丙啶基精胺(bisaziridinylspermine)；双奈法德(bisnafide)；(bistratene A)；比折來新(bizelesin)；(breflate)；溴匹立明(bropirimine)；布度鈦(budotitane)；丁硫氨酸亞碸亞胺(buthionine sulfoximine)；卡泊三醇(calcipotriol)；卡弗他丁C(calphostin C)；喜樹鹼衍生物；(canarypox IL-2)；capecitabine)；甲醯胺-胺基-三唑；羧醯胺基三唑；CaRest M3；CARN 700；軟骨衍生的抑制劑；卡折來新(carzelesin)；酪蛋白激酶抑制劑(ICOS)；栗精胺(castanospermine)；殺菌肽(cecropin B)；西曲瑞克(cetrorelix)；綠素類(chlorins)；氯喹噁啉磺醯胺；西卡前列素(cicaprost)；順式-吡喀紫質(cis-porphyrin)；順鉑(cisplatin)；克拉屈濱(cladribine)；氯米芬類似物(clomifene analogues)；克黴唑(clotrimazole)；(collismycin A)；(collismycin B)；考布他汀A4(combretastatin A4)；考布他汀類似物(combretastatin analogue)；(conagenin)；(crambescidin 816)；(crisnatol)；念珠藻環肽8(cryptophycin 8)；念珠藻環肽A(cryptophycin A)衍生物；(curacin A)；環戊蒽醌類(cyclopentanthraquinones)；(cycloplatam)；(cypernycin)；阿糖胞苷十八烷基磷酸鹽(cytarabine ocfosfate)；細胞溶解因子；細胞生長抑制素(cytostatin)；達昔單抗(dacliximab)；地西他濱(decitabine)；脫氫膜海鞘素(dehydrodidemnin B)；地洛瑞林(deslorelin)；地塞米松(dexamethasone)；右異環磷醯胺(dexifosfamide)；右雷佐生(dexrazoxane)；右維拉帕米(dexverapamil)；地阿巴隆(diaziquone)；代代寧(didemnin B)；(didox)；二乙基去甲精胺(diethylnorspermine；二氫-5-氮雜胞苷；(9-dioxamycin)；二苯基螺莫司汀(diphenyl spiromustine)；正二十二醇(docosanol)；多拉司瓊(dolasetron)；去氧氟尿苷(doxifluridine)；屈洛昔芬(droloxifene)；屈大麻酚(dronabinol)；倍癌黴素(duocarmycin)SA；依布硒(ebselen)；依考莫司汀(ecomustine)；依地福新(edelfosine)；依决洛單抗(edrecolomab)；(eflomithineklerriene)；乙嘧替氟(emitefur)；表柔比星(epirubicin)；愛普列特(epristeride)；厄洛替尼(erlotinib)；雌莫司汀(estramustine)類似物；雌激素促效劑；雌激素拮抗劑；依他硝唑(etanidazole)；依托泊苷磷酸鹽(etoposide phosphate)；依西美坦(exemestane)；法倔唑(fadrozole)；法扎拉濱(fazarabine)；芬維A胺(fenretinide)；非格司亭(filgrastim)；非那甾胺(finasteride)；夫拉平度(flavopiridol)；氟卓斯汀(flezelastine)；(fluasterone)；氟達拉濱(fludarabine)；氟唐黴素鹽酸鹽(fluorodaunoruriicin hydrochloride)；福酚美克(forfenimex)；福美坦(formestane)；福司曲星(fostriecin)；福莫司汀(fotemustine)；泰克薩菲瑞釓(gadolinium texaphyrin)；硝酸鎵；加洛他濱(galocitabine)；加尼瑞克(ganirelix)；吉非替尼(gefitinib)；明膠酶抑制劑；吉西他濱(gemcitabine)；麩胱甘肽抑制劑；(hepsulfam)；(heregulin)；六亞甲基二乙醯胺；金絲桃素(hypericin)；伊班膦酸(ibandronic acid)；伊達比星(idarubicin)；艾多昔芬(idoxifene)；伊决孟酮(idramantone)；伊莫福新(ilmofosine)；伊洛馬司他(ilomastat)；咪唑并吖啶酮(imidazoacridones)；咪喹莫特(imiquimod)；免疫刺激肽；類胰島素生長因子-1受體抑制劑；干擾素促效劑；干擾素；介白素；碘苄胍(iobenguane)；碘阿黴素(iododoxorubicin)；甘薯苦醇4-(ipomeanol,4-)；伊羅普拉(iroplact)；伊索拉定(irsogladine)；異康唑(isobengazole)；(isohomohalicondrin B)；伊他司瓊(itasetron)；(jasplakinolide)；(kahalalide F)；層狀素-N三乙酸鹽(lamellarin-N triacetate)；蘭瑞肽(lanreotide)；拉帕替尼(lapatinib)；(leinamycin)；來諾拉提(lenograstim)；香菇多糖硫酸鹽(lentinan sulfate)；(leptolstatin)；來曲唑(letrozole)；白血病抑制因子；白細胞α干擾素；柳菩林(leuprolide)+雌激素+黃體素；亮丙瑞林(leuprorelin)；左旋咪唑(levamisole)；利阿唑(liarozole)；直鏈多胺類似物；親脂性雙醣肽；親脂性鉑化合物；(lissoclinamide 7)；洛鉑(lobaplatin)；蚯蚓磷脂(lombricine)；洛美曲索(lometrexol)；氯尼達明(lonidamine)；洛索蒽醌(losoxantrone)；洛伐他汀(lovastatin)；洛索立賓(loxoribine)；勒托替康(lurtotecan)；莫特沙芬鑥(lutetium texaphyrin)；利索茶鹼(lysofylline)；裂解肽(lytic peptides)；美坦辛(maitansine)；甘露糖苷酶素A(mannostatin A)；馬立馬司他(marimastat)；馬索羅酚(masoprocol)；乳腺絲抑蛋白(maspin)；基質溶素(matrilysin)抑制劑；基質金屬蛋白酶抑制劑；美諾立爾(menogaril)；(merbarone)；美替瑞林(meterelin)；甲硫胺酸酶；氧氯普胺(metoclopramide)；MIF抑制劑；美服培酮(mifepristone)；米替福新(miltefosine)；米立司亭(mirimostim)；錯配雙股RNA；米托胍腙(mitoguazone)；二溴脫氧己六醇(mitolactol)；絲裂黴素類似物(mitomycin analogues)；米托萘胺(mitonafide)；米托毒素(mitotoxin)纖維母細胞生長因子-皂草素；米托蒽醌(mitoxantrone)；莫法羅汀(mofarotene)；莫拉司亭(molgramostim)；單株抗體，人類絨毛膜性腺激素；單磷醯脂質A+(niyobacterium)細胞壁sk；莫哌達醇(mopidamol；多重抗藥性基因抑制劑；多腫瘤抑制因子1-之治療；芥末抗癌劑；(mycaperoxide B；分枝桿菌細胞壁萃取物；美替拉酮(myriaporone)；N-乙醯基半胱胺素(acetyldinaline)；N-經取代苯甲醯胺；那法瑞林(nafarelin)；(nagrestip)；納洛酮(naloxone)+潘他唑新(pentazocine)；(napavin)；萘萜二醇(naphterpin)；那托司亭(nartograstim)；奈達鉑(nedaplatin)；奈莫柔比星(nemorubicin)；奈立膦酸(neridronic acid)；中性內肽酶；尼鲁米特(nilutamide)；(nisamycin)；氧化氮調節劑；氧化亞氮抗氧化劑；(nitrullyn)；O6-苯甲基鳥糞嘌呤；奧曲肽(octreotide)；(okicenone)；寡核苷酸；奧那司酮(onapristone)；恩丹西酮(ondansetron)；(oracin)；口服細胞激素誘發劑；奧馬鉑(ormaplatin)；奧沙特隆(osaterone)；奧沙利鉑(oxaliplatin)；(oxaunomycin)；(palauamine)；棕櫚醯基根瘤菌素(palmitoylrhizoxin)；帕米膦酸(pamidronic acid)；人参炔三醇(panaxytriol)；帕諾米芬(panomifene)；副球菌素(parabactin)；帕折普汀(pazelliptine)；培門冬酶(pegaspargase)；培得星(peldesine)；戊聚醣聚硫酸鈉；(pentostatin)；潘曲唑(pentrozole)；全氟溴烷(perflubron)；培磷醯胺(perfosfamide)；紫蘇醇(perillyl alcohol)；苯連氮黴素(phenazinomycin)；苯乙酸酯；磷酸酶抑制劑；必醫你舒(picibanil)；毛果芸香鹼鹽酸鹽(pilocarpine hydrochloride)；吡柔比星(pirarubicin)；吡曲克辛(piritrexim)；(placetin A)；(placetin B)；纖維蛋白溶酶原活化物抑制劑；鉑錯合物；鉑化合物；鉑-三胺錯合物；卟吩姆鈉(porfimer sodium)；紫菜黴素(porfiromycin)；潑尼松(rednisone)；丙基雙吖啶酮(propyl bis-acridone)；前列腺素J2，蛋白酶體抑制劑；蛋白A源性免疫調節劑；蛋白激酶C抑制劑；蛋白激酶C抑制劑，微藻(microalgal)；蛋白酪胺酸磷酸酶抑制劑；嘌呤核苷磷酸化酶抑制劑；紅紫素(purpurin)；吡唑啉吖啶(pyrazoloacridine)；吡多醛-血红蛋白-聚氧乙烯結合物(pyridoxylated hemoglobin polyoxyethylene conjugate)；raf拮抗劑；雷替曲塞(raltitrexed)；(rarnosetran)；ras法呢基蛋白轉移酶抑制劑；ras抑制劑；ras-GAP抑制劑；去甲基化瑞替普汀(retelliptine)；依替膦酸錸Re 186(rhenium Re 186 etidronate)；根瘤菌素(rhizoxin)；核酶(ribozymes)；RII維甲醯酚胺(retinamide)；洛太米特(rogletimide)；羅希吐鹼(rohitukine)；羅莫肽(romurtide)；羅喹美克(roquinimex)；(rubiginone B1)；(ruboxyl)；沙芬戈(safingol)；聖多平(saintopin)；SarCNU；肌植醇A(Sarcophytol A)；沙格司亭(sargramostim)；Sdi 1模擬物；司莫司汀(semustine)；衰老衍生抑制劑1；/正義寡核苷酸；訊號傳遞抑制劑；訊號傳遞調節劑；單鏈抗原結合蛋白；西佐喃(sizofuran)；索布佐生(sobuzoxane)；硼卡鈉(sodium borocaptate)；苯乙酸鈉；(solverol)；體介素(somatomedin)結合蛋白；(sonerrnin)；膦門冬酸(sparfosic acid)；穗黴素D(spicamycin D)；螺莫司汀(spiromustine)；脾臟五肽(splenopentin)；海綿抑制素1(spongistatin 1)；角鯊胺(squalamine)；幹細胞抑制劑；幹細胞分化抑制劑；(stipiamide)；基質溶素(stromelysin)抑制劑；(sulfinosine)；超活化血管活性腸肽拮抗劑；(suradista)；蘇拉明(suramin)；苦馬豆素(swainsonine)；合成的葡萄糖胺聚糖；(tallimustine)；他莫昔芬甲碘化物(tamoxifen methiodide)；牛磺莫司汀(tauromustine)；他扎羅汀(tazarotene)；替可加蘭鈉(tecogalan sodium)；替加氟(tegafur)；(tellurapyrylium)；端粒酶抑制劑；替莫泊芬(temoporfin)；替莫唑胺(temozolomide)；替尼泊苷(teniposide)；十氧化四氯(tetrachlorodecaoxide)；(tetrazomine)；菌體胚素(thaliblastine)；噻可拉林(thiocoraline)；血小板生成素(thrombopoietin)；血小板生成素模擬物；胸腺法新(thymalfasin)；胸腺生成素(thymopoietin)受體促效劑；胸腺曲南(thymotrinan)；促甲狀腺激素；乙基紅紫素錫(tin ethyl etiopurpurin)；替拉扎明(tirapazamine)；二氯二茂鈦(titanocene bichloride)；(topsentin)；托瑞米芬(toremifene)；全能的幹細胞因子；轉譯抑制劑；維甲酸(tretinoin)；三乙醯尿苷(triacetyluridine)；曲西立濱(triciribine)；三甲曲沙(trimetrexate)；曲普瑞林(triptorelin)；托烷司瓊(tropisetron)；妥羅雄脲(turosteride)；酪胺酸激酶抑制劑；酪胺酸磷酸化抑制劑(tyrphostins)；UBC抑制劑；(ubenimex)；尿殖竇衍生生長抑制因子；尿激酶受體拮抗劑；伐普肽(vapreotide)；(variolin B)；載體系統，紅血球基因治療；維拉雷瑣(velaresol)；藜蘆胺(veramine)；(verdins)；維替泊芬(verteporfin)；長春瑞濱(vinorelbine)；(vinxaltine)；(vitaxin)；伏氯唑(vorozole)；扎諾特隆(zanoterone)；折尼鉑(zeniplatin)；亞苄維C(zilascorb)；及凈司他丁斯酯(zinostatin stimalamer)。另外較佳的抗癌藥為5-氟尿嘧啶及甲醯四氫葉酸(leucovorin)。
根據本發明，抗癌劑可為治療用抗體，其包括(但不限於)HERCEPTIN(曲妥珠單抗(Trastuzumab))(Genentech,CA)，一種用於治療乳癌轉移病患之人源化抗-HER2單株抗體；REOPRO(阿昔單抗(abciximab))(Centocor)，一種用於預防血栓形成之血小板上的抗-糖蛋白IIb/IIIa受體；ZENAPAX(達利珠單抗(daclizumab))(Roche Pharmaceuticals,Switzerland)，一種用於預防急性腎臟同種異體移植排斥之免疫抑制、人源化抗-CD25單株抗體；PANOREX，一種鼠科抗-17-IA細胞表面抗原IgG2a抗體(Glaxo Wellcome/Centocor)；BEC2，一種鼠科抗-個體遺傳型(GD3抗原決定區)IgG抗體(ImClone System)；IMC-C225，一種嵌合抗-EGFR IgG抗體(ImClone System)；VITAXIN，一種人源化抗-.α.V.β.3整合素抗體(Applied Molecular Evolution/MedImmune)；Campath 1H/LDP-03，一種人源化抗CD52 IgG1抗體(Leukosite)；Smart M195，一種人源化抗-CD33 IgG抗體(Protein Design Lab/Ranebo)；RITUXAN，一種嵌合抗-CD20 IgG1抗體(IDEC Pharm/Genentech,Roche/Zettyaku)；LYMPHOCIDE，一種人源化抗-CD22 IgG抗體(Immunomedics)；LYMPHOCIDEY-90(Immunomedics)；Lymphoscan(Tc-99m-標定；放射顯影；Immunomedics)；Nuvion(抗CD3；Protein Design Labs)；CM3，一種人源化抗-ICAM3抗體(ICOS Pharm)；IDEC-114，一種靈長類化抗-CD80抗體(IDEC Pharm/Mitsubishi)；ZEVALIN，一種放射性標定之鼠科-CD20抗體(IDEC/Schering AG)；IDEC-131，一種人源化抗-CD40L抗體(IDEC/Eisai)；IDEC-151，一種靈長類化抗-CD4抗體(IDEC)；IDEC-152，一種靈長類化抗-CD23抗體(IDEC/Seikagaku)；SMART抗-CD3，一種人源化抗-CD3 IgG(Protein Design Lab)；5G1.1，一種人源化抗-補體因子5(C5)抗體(Alexion Pharm)；D2E7，一種人源化抗-TNF-α抗體(CAT/BASF)；CDP870，一種人源化抗-TNF-αFab斷片(Celltech)；IDEC-151，一種靈長類化抗-CD4 IgG1抗體(IDEC Pharm/SmithKline Beecham)；MDX-CD4，一種人類抗-CD4 IgG抗體(Medarex(Eisai/Genmab)；CD20-鏈黴親和素(sreptdavidin)(+生物素-釔90；NeoRx)；CDP571，一種人源化抗-TNF-αIgG4抗體(Celltech)；LDP-02，一種人源化抗-α-4-β-7抗體(LeukoSite/Genentech)；OrthoClone OKT4A，一種人源化抗-CD4 IgG抗體(Ortho Biotech)；ANTOVA，一種人源化抗-CD40L IgG抗體(Biogen)；ANTEGREN，一種人源化抗-VLA-4 IgG抗體(Elan)；及CAT-152，一種人類抗-TGF-β2抗體(Cambridge Ab Tech)。
在另一實施例中，抗癌劑可由下列各物組成之群中選出：順鉑、吉非替尼、拉帕替尼及厄洛替尼。
本發明係評估GMI對癌細胞侵襲和轉移(特別是EGF-引起的癌細胞侵襲和轉移)之抑制效果及探討所涉及的分子機制。本發明驗證了EFG處理使得PI3K/Akt增加，而導致Rac1/Cdc42活性下調及細胞和細胞接觸集結，以及腫瘤細胞入侵增強。GMI抑制了涉及PI3K/Akt和Stat3路徑之EGF-引起的549細胞遷移和侵襲。再者，GMI可抑制TNF-α引發的MMP9蛋白酶活性。
無需進一步詳述，咸信熟習本項技術者可在前面說明之基礎上充分地利用本發明。因此，下列實例應僅視為說明之用而並非在任何方面限制本發明之範圍。。
重組的EGF係購自Peprotech公司。AG1478係得自Calbiochem。用於西方墨點之抗磷酸化-專一性EGFR Y1068(ab40815)和cdc42(ab41429)抗體係得自Abcam。抗-磷酸化STAT3 Y705(#9131)、抗-磷酸化GSK-3β(#9336)及抗-磷酸化Akt Ser473(#9271)係購自Cell Signaling公司。其他的抗體包括抗-β肌動蛋白單株抗體(Sigma)及Rac1抗體(Upstate)。由Mycomagic Biotechnology公司所製造的GMI係由小孢子靈芝所產生及經改良。
人類肺癌細胞株A549[美國菌種保存中心(ATCC)；CCL-185]係得自ATCC。將細胞置於添加經熱去活化的胎牛血清(FBS；Life Technologies)以及青黴素和鏈黴素(各100 mg/mL)之DMEM(Life Technologies)中以37℃於5% CO2
濕化的大氣中生長。
小細胞肺癌中EGFR之表現先前已說明過(Jaramillo等人,2008,Cancer Biol Ther
,7,557-568)。為了瞭解GMI對EGF-促進的A549細胞遷移之抑制效用，係進行GMI對EGF-引發的細胞移動和傷口癒合分析之效用研。
傷口癒合分析，係將癌細胞置於24-孔盤上以含10% FBS之培養基培養並使其生長至細胞單層近乎全滿。使用塑膠微量吸管在各孔槽的單層細胞上劃一道「傷口」。然後將單層細胞以PBS清洗二次移除碎片和分離的細胞，並加入不同濃度的GMI(0、2、4和8 mg/mL)。將PBS加到各對照的孔槽中作為溶劑對照組。培養24小時後，將細胞以PBS清洗二次，以95%酒精固定並以10% Giemsa溶液(Merck)染色。然後以光學顯微鏡拍攝細胞(放大倍數,X 200)。實驗係進行三重複。以2-8 μg/ml的GMI培養24 h後，拍攝遷移到去裸帶的細胞。結果驗證GMI係以劑量依賴抑制549細胞遷移至去裸帶(圖1A)。相對的，僅以EGF處理之細胞在治療後24 h顯示傷口閉合加速(圖1A)。以EGF和GMI共處理之細胞，顯現傷口閉合活性顯著降低(圖1A)。在另一方面，AG1478，EGF之正對照，能抑制EGFR的磷酸化作用。AG1478抑制EGF-引起的遷移係與GMI相類似(圖1B)。
細胞侵襲分析係使用直徑6.5 mm，以10 mm厚多孔(8 μm)聚碳酸酯膜分開成二層之修改過的博登移形器(Boyden chamber)來進行(Transwell；Costar,Cambridge,MA)。於膜的上層塗覆基質膠(Matrigel)(0.3 mg/mL；BD Biosciences Discovery Labware)計3小時。由A549細胞製備條件培養基，其中A549細胞係有或無以GMI、LY294002(50μM)或AG1478(2 μM)預處理8 h。於下層的培養基中加入含EGF(10 ng/ml)之10% FBS-DMEM或條件培養基。將細胞胰酶化、離心並以4 X 105
細胞/mL再懸浮於0.5% FBS-DMEM中。培養24 h後，將上孔槽的細胞及塗覆基質膠的膜以甲醇固定，並以20% Giemsa溶液(Merck)染色。將黏附在聚碳酸酯過濾膜下表面的細胞於光學顯微鏡下(放大倍數,X 100)計數。實驗係進行三重複。
腫瘤細胞之侵襲能力為癌症轉移重要的特徵之一。博登移行器係經修改以定量A549細胞之侵襲潛力。結果顯示，隨著GMI濃度的增加，GMI引發了劑量依賴之侵襲性降低(圖2A)。在4 μg/ml時侵襲性降至22%(侵襲的細胞數由1895±37降至419±6)，及在16 μg/ml時侵襲性降至9%以下(侵襲的細胞數由1895±37降至61±3)。隨後，GMI對EGF-提升的侵襲性引發了劑量依賴性的降低(圖2A)。在4 μg/ml時侵襲性降至52%(侵襲的細胞數由2515±212降至1306±30)，及在16 μg/ml時侵襲性降至5%以下(侵襲的細胞數由2515±212降至121±39)。結果驗證GMI顯著地抑制了EGF-所提升的A549細胞侵襲性。
已有數個研究指出轉錄因子p38 MAPK、Stat3和Akt涉及不同細胞類型之細胞轉移活性(Broadbelt等人,2009,Am J Physiol Renal Physiol
,297,F114-124；Lee等人,2008,Toxicol Appl Pharmacol
,226,178-191；Shih等人,2009,Food Chem Toxicol
,47,1985-1995)。Akt係作用在PI3K之下游。其為細胞存活、生長及侵襲之一多功能調節子，並在經EGF刺激的10分鐘內磷酸化。這些觀察暗示，由EGF引起之Akt活化在A549細胞侵襲活性佔有一席之地。
於RIPA緩衝液中製備總細胞解離液(100 μl置於60mm培養皿中)。將50μg的解離液裝載至8%聚丙烯醯胺凝膠上並以SDS凝膠電泳分析。轉移到PVDF(Amersham)後，將墨點以含有0.2% Tween-20之5%脫脂奶TBS溶液(10 mM Tris-CL pH7.5,150 mM NaCl)進行阻斷。以溶於5%脫脂奶之TBS溶液的抗體(以其建議的稀釋倍數)於4℃將墨點進行探針探測至隔夜。以結合二級抗體之適合的辣根過氧化酶(Cell Signaling)偵測後，根據製造商的說明(Perkin Elmer Life Sciences)藉由增強化學發光使墨點顯現。所有的實驗皆進行雙重複。
將細胞以PBS清洗二次並以3.7%多聚甲醛-PBS溶液於室溫固定10分鐘。再以PBS清洗二次後，以0.1% Triton X-100之PBS溶液將細胞穿孔3至5分鐘並再次以PBS清洗。使用Texas Red-X phalloidin(2單位/mL)及Alexa Fluor 488 DNase I結合物(9 μg/mL)定位肌動蛋白絲(F-肌動蛋白)和G-肌動蛋白。以阻斷溶液(1%牛血清白蛋白及0.025%皂素之PBS溶液)稀釋螢光染劑並於室溫加到蓋玻片放置60分鐘。以PBS清洗三次後，以含DAPI(Life Technologies)之Prolong Gold抗淬滅劑蓋封在顯微鏡載片上。以X 400放大倍數之共軛焦雷射掃描顯微鏡(ZEISS LSM510 BETA)，進行F-肌動蛋白細胞骨架之造影。
為了評估GMI是否媒介及/或抑制Akt和Stat3之磷酸化，本發明係於經不同濃度GMI處理8 h之A549細胞中就GMI對Akt和Stat3的磷酸化狀態之效應進行研究。圖3顯示GMI顯著地抑制EGF-引起的EGFR和Akt之活化，然而其對Stat3僅有極小的效用。
EGF主要係經由其細胞表面受體EGFR之活化引發細胞增生和遷移。Rac1活化訊號傳遞路徑係位於EGFR之下游(Binker等人,2009,Biochem Biophys Res Commun
,379,445-450)。
活化的Rac1和Cdc42係藉由沉降分析(pull-down assay)來測定(Binker等人,2009,Biochem Biophys Res Commun
,379,445-450)。將經無血清培養之A549細胞有或無以EGF刺激3分鐘，及然後收集至800 μl冰冷的裂解緩衝液中。將裂解液離心以移除細胞碎片。從各上清液取出5 μl，以蛋白分析套組測量蛋白含量(Bio-Rad,Hercules,CA)。取出20μl測定總裂解液中之總Rac1，並將剩餘的量於用沉降分析。然後將含有等量蛋白之裂解液與15 μg的GST-PAK-PBD-微珠(Pierce)混合。將總Rac1和Cdc42之裂解液樣本及顆粒微珠置於Laemmli樣本-緩衝液中稀釋並煮沸。使用SDS-PAGE(12%凝膠)分離蛋白質。轉載至硝基纖維素膜(Bio-Rad)後，以牛血清白蛋白阻斷墨點，接著以Rac1抗體培養至隔夜。使用過氧化酶偶聯抗小鼠抗體和化學發光法(Perkin Elmer Life Sciences)使抗體的結合顯現出。藉由相當於總裂解液之再探測膜，以抗-β-肌動蛋白抗體(為顯示出)驗證是否已等載(Equal loading)。
評估GMI對Rac1活性之效應，以測定GMI抗侵襲效應和Rac1/Cdc42訊號傳遞路徑間的關係。如圖5(通路1和2)所示，以10 ng/ml EGF處理3分鐘，引發Rac1和Cdc42活性。相反的，GMI以劑量依賴的方式降低了EGF-所提升的Cdc42活性，而A549細胞之Rac1活性僅小量下降(圖5，第2道至第4道)。然而，Rac1活性係直接與細胞移動力相關。
了解肌動蛋白細胞骨架為細胞侵襲一重要決定因子，本發明下一步係於帶有EGF之經GMI-處理的細胞中，分析G-肌動蛋白和F-肌動蛋白的細胞骨架架構(Denys等人,2008,Cancer Lett
,266,263-274)。EGF在乳癌的進程扮演著重要角色，並如前面所示(Lu等人,2003,Cancer Cell
,4,499-515)。以10 ng/ml的EGF處理72 h以上，可引發A431細胞之EMT。如圖6所示，在此研究中EGF引發F-肌動蛋白纖維(紅色)及增加G-肌動蛋白纖維(綠色)。在以EGF處理24小時的A549細胞中觀察到層狀偽足(Lamellipodia)形成。在經EGF處理或單獨經GMI處理之549細胞中，GMI消除了F-肌動蛋白和G-肌動蛋白之延長和聚合化。以劑量依賴的方式及以組合治療，GMI亦降低集中接觸的大小。
將CaLu-1細胞以各種濃度的順鉑(0、2.5、5、10、20 μM)和小孢子靈芝GMI(0、4、8和16 μg/mL)共處理48 h，接著以MTT分析估算細胞存活力。以順鉑和GMI共處理後測定增效效應。
MTT分析係用來測定GMI和順鉑對Calu-1細胞增生之效應。在代謝活耀的細胞中，MTT(噻唑藍溴化四唑)(Sigma)藉由去氫酶酵素還原成甲臢(formazan)產物。添加100 μl DMSO後，直接測量96-孔分析盤於570 nm之吸收度。甲臢之量係視為與培養中存活的細胞數成正比。
簡言之，將細胞(5×103
)置於含200 μl生長培養基之96-孔盤上培養。培養24 h後，小心地移除培養基並於孔槽中加入100 μl含各種濃度GMI之新鮮的培養基。細胞係以0、4、8、16 μg/ml之GMI和0、2.5、5、10 μM之順鉑處理48 h。在此步驟終了時，加入100 μl/孔之0.5 mg/ml MTT溶液並將孔槽於37℃濕化的培養箱中培養3 h。將上清液丟棄並於其中加入100 μl DMSO以溶解甲臢。於VERSAmax微量盤判讀機以570 nm分析吸收度。吸收值係以各處理三重複的平均值±SE表示。包括對照組的細胞和化合物。未經處理的細胞之吸收度視為100%。
如圖7所示，GMI和順鉑之組合展現增效效應，且當與GMI組合使用時，順鉑之量可大大降低。例如，2.5 μM順柏與16 μg/ml GMI組合可達到約50%細胞存活率，而單獨使用順鉑則需約10 μM才能達到相同的存活率。
<110> 蘑法生物科技股份有限公司
<120> 小孢子靈芝免疫調節蛋白(GMI)之新用途
<130> M52295/US1549
<140> 099142868
<141> 2010-12-08
<150> 12/826,230
<151> 2010-06-29
<160> 3
<170> PatentIn version 3.4
<210> 1
<211> 6
<212> PRT
<213> 小孢子靈芝(Ganoderma microsporum)
<400> 1
<210> 2
<211> 10
<212> PRT
<213> 小孢子靈芝(Ganoderma microsporum)
<400> 2
<210> 3
<211> 111
<212> PRT
<213> 小孢子靈芝(Ganoderma microsporum)
<400> 3
圖1係顯示GMI和AG1478抑制A549細胞之癌細胞遷移。A549細胞(1.2 X 105
細胞/24孔)係以劑量增加的GMI(2、4、8 μg/ml)處理24 h。進行傷口癒合分析以評估(A)GMI或(B)AG1478對A549細胞遷移之抑制效應。將全滿的A549單層細胞劃出缺痕，及以(A)GMI或(B)AG1478處理24 h後，以顯微鏡監看修復狀況。以虛線作為計時起點，計算遷移到傷口區域的細胞。
圖2係顯示GMI抑制EGF-引起的A549細胞侵襲。將A549細胞(2 X 104
細胞/孔)植入膜的上層並以不同濃度的GMI(4、8、16 μg/ml)處理2小時。下層填入添加10 ng/ml或100 ng/ml EGF之DMEM。約24 h後，侵入的A549細胞通過該膜，並計算遷移至膜上的細胞來定量。將細胞固定、染色及如文中所述計數。數據係以平均值±SD表示。
圖3係顯示GMI對A549細胞訊號傳導路徑之效應。將A54細胞(5 X 105
細胞/60 mm)以各種濃度的GMI(4、16 μg/ml)或AG1478(EGFR抑制劑)預處理8小時，之後以EGF(如所示)培養10分鐘。將細胞裂解液以磷酸化-專一性EGFR(Y1068)(A和B)、抗-磷酸化-AKT(A)、抗-AKT(A)、抗-磷酸化-GSK3β(A)或抗-磷酸化-STAT3抗體(B)進行免疫印跡。以西方墨點抗β-肌動蛋白(A和B)測定蛋白裝填。
圖4係顯示GMI、PI3K抑制劑和EGFR抑制劑對EGF-引發的A549細胞侵襲之效應。將EGF(10 ng/ml)塗覆在下層作為趨化劑。將經無血清培養的細胞(2 X 104
細胞/孔)種入由塗覆基質膠基(Matrigel)底膜基質之8-μm孔徑的過濾器所組成的上層，及然後以8 μg/ml GMI、50 μM Ly294002(PI3K抑制劑)或2 μM AG1478(EGFR抑制劑)培養24 h。於光顯微鏡下計算侵襲膜下表面之細胞。數據係以平均值±SD表示。
圖5係顯示GMI抑制EGF-引起的Cdc42活化。將A549細胞種入100 mm盤並培養至約80%的滿度。然後將細胞以各種劑量的GMI(4、16μg/ml)處理。GMI抑制了Cdc42活化，但對Rac1僅具極小效用。將A549細胞以各種濃度的GMI預處理24 h，之後以10 ng/mL EGF刺激3分鐘。之後，將細胞以冷的PBS清洗並置於RIPA緩衝液盤中裂解。使用固定在麩胱甘肽微珠上之PAK1的GST-PBD融合蛋白沉降活化的GTP-結合Rac1或Cdc42並以抗-Rac1和抗-Cdc42抗體偵測活化的Rac1和Cdc42。
圖6係顯示GMI對EGF-引發的F-肌動蛋白/G-肌動蛋白比例和絲狀偽足(filopodia)形成之效應。將A549細胞(1 X 104
細胞/孔)種入附蓋的24孔盤中。將A549細胞以各種濃度的GMI(2、4、8μg/ml)預處理1 h，之後以10 ng/mL EGF刺激23 h。將有或無經EGF處理的A549細胞以Texas Red-X鬼筆環肽(phalloidin)和Alexa Fluor 488 DNase I結合物染色以偵測F-肌動蛋白(紅色)和G-肌動蛋白(綠色)。以Texas Red-X鬼筆環肽標定的F-肌動蛋白顯示，A549細胞出現許多絲狀偽足，而經GMI-處理的細胞則出現較少的絲狀偽足纖維。
圖7係顯示順鉑和GMI共處理對CaLu-1細胞存活力之效應。
(無元件符號說明)
Claims (13)
- 一種小孢子靈芝(Ganoderma microsporum )免疫調節蛋白(GMI)或其重組物於製備抑制癌細胞中EGF受體活性之藥劑之用途，其中該GMI具有(1) -Leu-Ala-Trp-Asn-Val-Lys-(LAWNVK；SEQ ID NO：1)及(2) -Asp-Leu-Gly-Val-Arg-Pro-Ser-Tyr-Ala-Val-(DLGVRPSYAV；SEQ ID NO：2)之胺基酸序列或具有如MSDTALIFTLAWNVKQLAFDYTPNWGRGRPSSFIDTVTFPTVLTDKAYTYRVVVSGKDLGVRPSYAVESDGSQKINFLEYNSGYGIADTNTIQVYVIDPDTGNNFIVAQWN(SEQ ID NO：3)之胺基酸序列。
- 一種小孢子靈芝免疫調節蛋白(GMI)於製備治療EGF受體活性介導之癌細胞侵襲和轉移之藥劑之用途，其中該GMI具有(1) -Leu-Ala-Trp-Asn-Val-Lys-(LAWNVK；SEQ ID NO：1)及(2) -Asp-Leu-Gly-Val-Arg-Pro-Ser-Tyr-Ala-Val-(DLGVRPSYAV；SEQ ID NO：2)之胺基酸序列或具有如MSDTALIFTLAWNVKQLAFDYTPNWGRGRPSSFIDTVTFPTVLTDKAYTYRVVVSGKDLGVRPSYAVESDGSQKINFLEYNSGYGIADTNTIQVYVIDPDTGNNFIVAQWN(SEQ ID NO：3)之胺基酸序列。
- 如請求項2之用途，其中該癌細胞係來自肺癌、肺，頭和頸之鱗狀細胞癌、乳癌膀胱癌、腦癌、肝癌或大腸癌。
- 如請求項3之用途，其中該肺癌為非小細胞肺癌(NSCLC)。
- 如請求項2之用途，其中該GMI係以非經腸給藥。
- 如請求項2之用途，其中該GMI係以口服或直腸給藥。
- 如請求項2之用途，其中該GMI係用於癌症化學預防。
- 如請求項2之用途，其中該GMI可與放射性治療和化療組合給藥。
- 如請求項2之用途，其中該GMI可進一步與一抗癌劑同時、連續或分開投予。
- 如請求項9之用途，其中該癌細胞係來自肺癌、肺，頭和頸之鱗狀細胞癌、乳癌、膀胱癌、腦癌、肝癌或大腸癌。
- 如請求項10之用途，其中該肺癌為非小細胞肺癌(NSCLC)。
- 如請求項9之用途，其中該抗癌劑係由下列各物組成之群中選出：順鉑(cisplatin)吉西他濱(gemcitabine)；碘阿黴素(iododoxorubicin)；奥馬鉑(ormaplatin)；奥沙利鉑(oxaliplatin)；鉑錯合物；鉑化合物；鉑-三胺錯合物；長春瑞濱(vinorelbine)；折尼鉑(zeniplatin)；吉非替尼(gefitinib)、拉帕替尼(lapatinib)及厄洛替尼(erlotinib)。
- 一種醫藥組成物，其包括小孢子靈芝(Ganoderma microsporum )免疫調節蛋白(GMI)或其重組物及一抗癌劑；其中該GMI具有(1) -Leu-Ala-Trp-Asn-Val-Lys-(LAWNVK；SEQ ID NO：1)及(2) -Asp-Leu-Gly-Val-Arg-Pro-Ser-Tyr-Ala-Val-(DLGVRPSYAV；SEQ ID NO：2)之胺基酸序列或具有如MSDTALIFTLAWNVKQLAFDYTPNWGRGRPSSFIDTVTFPTVLTDKAYTYRVVVSGKDLGVRPSYAVESD GSQKINFLEYNSGYGIADTNTIQVYVIDPDTGNNFIVAQWN(SEQ ID NO：3)之胺基酸序列；及其中該抗癌劑係由下列各物組成之群中選出：順鉑(cisplatin)吉西他濱(gemcitabine)；碘阿黴素(iododoxorubicin)；奥馬鉑(ormaplatin)；奥沙利鉑(oxaliplatin)；鉑錯合物；鉑化合物；鉑-三胺錯合物；長春瑞濱(vinorelbine)；折尼鉑(zeniplatin)；吉非替尼(gefitinib)、拉帕替尼(lapatinib)及厄洛替尼(erlotinib)。
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| TWI702291B (zh) * | 2018-12-28 | 2020-08-21 | 薩摩亞商康多富國際有限公司 | 個人化癌症保健食品組合的決定方法及非暫態電腦可讀取儲存媒體 |
| TWI702292B (zh) * | 2018-12-28 | 2020-08-21 | 薩摩亞商康多富國際有限公司 | 個人化新陳代謝疾病保健食品組合的決定方法及非暫態電腦可讀取儲存媒體 |
Families Citing this family (20)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US9161964B2 (en) * | 2010-06-29 | 2015-10-20 | Mycomagic Biotechnology Co., Ltd. | Uses of an immunomodulatory protein (GMI) from Ganoderma microsporum |
| US9018171B2 (en) * | 2010-06-29 | 2015-04-28 | Mycomagic Biotechnology Co., Ltd. | Uses of an immunomodulatory protein (GMI) from Ganoderma microsporum |
| TWI474831B (zh) * | 2012-09-14 | 2015-03-01 | Univ Taipei Medical | 免疫調節蛋白於促進傷口癒合或組織損傷治療的用途 |
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| US11141458B2 (en) * | 2019-07-17 | 2021-10-12 | Mycomagic Biotechnology Co., Ltd. | Composition and methods for promoting and treating chronic wound healing |
| EP3824901B1 (en) * | 2019-11-21 | 2026-04-29 | LEE, Feng-Chou | Pharmaceutical composition and use for applying ganoderma microsporum immunomodulatory protein and keyhole limpet hemocyanin in carcinoma treatment |
| AU2022274964A1 (en) * | 2021-05-11 | 2023-11-30 | Shaochi Hsin | Method for treatment of psoriasis |
| US12122809B2 (en) * | 2022-01-12 | 2024-10-22 | Mycomagic Biotechnology Co., Ltd. | Immunomodulatory protein for alleviation and/or treatment of coronavirus diseases |
| WO2023245160A1 (en) * | 2022-06-16 | 2023-12-21 | Astrid Pharma Corp. | Methods and compositions of quaternary immunomodulatory nanoparticles for medical applications and immunotherapy |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| TW200726775A (en) * | 2006-01-06 | 2007-07-16 | Biosoltech Internat Company Ltd | An immunomodulatory protein cloned from ganoderma microsporum |
Family Cites Families (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE3886986T2 (de) * | 1987-04-28 | 1994-08-11 | Meiji Milk Prod Co Ltd | Glykoprotein, Verfahren zu dessen Herstellung und dieses als aktiven Bestandteil enthaltendes immunsuppressives Agens. |
| US5844001A (en) * | 1993-02-26 | 1998-12-01 | Research Development Foundation | Combination platinum chemotherapeutic/antiestrogen therapy for human cancers |
| US7601808B2 (en) * | 2006-03-02 | 2009-10-13 | World Bio-Tech Alliance Corporation | Immunomodulatory protein cloned from ganoderma microsporum |
-
2010
- 2010-06-29 US US12/826,230 patent/US8476238B2/en active Active
- 2010-12-08 TW TW099142868A patent/TWI414307B/zh active
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| TW200726775A (en) * | 2006-01-06 | 2007-07-16 | Biosoltech Internat Company Ltd | An immunomodulatory protein cloned from ganoderma microsporum |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| TWI702291B (zh) * | 2018-12-28 | 2020-08-21 | 薩摩亞商康多富國際有限公司 | 個人化癌症保健食品組合的決定方法及非暫態電腦可讀取儲存媒體 |
| TWI702292B (zh) * | 2018-12-28 | 2020-08-21 | 薩摩亞商康多富國際有限公司 | 個人化新陳代謝疾病保健食品組合的決定方法及非暫態電腦可讀取儲存媒體 |
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