▎ Nchọpụta PNC 27
Gịnị bụ ngwa nke PNC-27?
1, Ọgwụgwọ ọrịa leukemia:
PNC-27 na-enwe ike ijikọ protein HDM-2 na akpụkpọ ahụ nke mkpụrụ ndụ kansa ma mee ka e nwee pores transmembrane cytotoxic. N'ime nnyocha nke ụmụ mmadụ na-abụghị stem cell nnukwu myeloid leukemia cell line, HDM-2 chọpụtara na a na-egosipụta nke ọma na akpụkpọ ahụ nke U937 (nnukwu monocytic leukemia), OCI-AML3 (nnukwu granulomonocytic leukemia), na HL60 (nnukwu promyelocytic leukemia) cell.PNC-27 na-ejikọta na HDM-27 membranes na nelaccrosis. dehydrogenase) hapụ n'ime awa 4. (LDH) wepụta n'ime awa 4. Ịtụle HDM-2 na akpụkpọ ahụ cell nwere ike ịbụ atụmatụ nwere ike ịgwọ ọrịa leukemia.PNC-27 gosipụtara ọrụ mgbochi ọrịa leukemia dị iche iche n'ọtụtụ ahịrị sel leukemia site n'ịchụso Membrane HDM-2 [1]..
2. Na-ebute mkpụrụ ndụ tumor lysis
Na-arụ ọrụ dị ka peptide na-adịghị mma:
Ọtụtụ nchọpụta egosila na PNC-27 na-ebute mkpụrụ ndụ tumor lysis dị ka peptide na-adịghị mma kama dị ka iberibe. Dịka ọmụmaatụ, n'ime nyocha nke mkpụrụ ndụ cancer ara MCF-7 na MCF-10-2A mammary epithelial cell na-agbanweghị, a na-emeso mkpụrụ ndụ na PNC-27 na-acha akwụkwọ ndụ akwụkwọ ndụ nke a na-akpọ amino terminus na red fluorescently labeled carboxy terminus. Nsonaazụ gosiri punctate odo fluorescence dị iche iche na akpụkpọ ahụ cell cancer na 30 min, na-egosi na peptide adịghị emebi emebi dị na akpụkpọ ahụ cell cancer ma na-abawanye na cell lysis. N'ụzọ dị iche, mkpụrụ ndụ MCF-10-2A na-agbanweghị agbanwe na mbụ gosipụtara fluorescence na-acha edo edo edo edo, mana emesịa pụọ. N'adịghị ka mkpụrụ ndụ kansa, mkpụrụ ndụ ndị a na-agbanweghị agbanwe nọgidere na-adị irè. Nke a na-egosi na PNC-27 na-ebute mgbawa akpụkpọ ahụ n'ime mkpụrụ ndụ kansa site n'ime ihe dị ka peptide dum, kama ịbụ iberibe ..
Na-ejikọta na HDM-2 iji mepụta ihe owuwu pore:
PNC-27 nwere HDM-2-binding structural domain na cell-penetrating peptide (CPP) presequence, nke na-eme ka e guzobe ihe owuwu pore site na ijikọta HDM-2 na akpụkpọ ahụ sel, na-eduga na lysis cell tumor na necrosis. Ngụkọta ike na-agbanwe agbanwe gosiri na PNC-27 na-etolite mgbagwoju anya na HDM-2 na nha 1: 1, yana usoro na-eduga na-atụ aka na mgbagwoju anya. Immunoscanning eletrọn microscopy ọmụmụ kpughere ọnụnọ nke otutu 6 nm na 15 nm akara ọla edo na nha nke ihe dịka 1: 1 na pores n'elu mkpụrụ ndụ kansa nke a na-emeso PNC-27, na-atụ aro na ogige ndị a dị mkpa maka nhazi pore. N'ụzọ dị iche, ọ dịghị pores e guzobere na njikwa, fibroblasts na-agbanweghị agbanwe na-emeso ya na PNC-27 [3].
Ọrịa cancer pancreatic:
Akwụkwọ akụkọ anticancer PNC-27 peptide na-ebute necrosis nke mkpụrụ ndụ kansa pancreatic MiaPaCa-2 mmadụ n'ụdị dabere na dose, mana ọ naghị egbu egbu na sel nkịtị. Nnyocha egosiwo na PNC-27, mgbe ejikọtara ya na Gemzar, onye na-ahụ maka chemotherapeutic eji agwọ ọrịa cancer pancreatic, nwere mmetụta cytotoxic dị ukwuu na mkpụrụ ndụ MiaPaCa-2 karịa Gemzar ma ọ bụ PNC-27 naanị. Nke a nwere ike ịbụ n'ihi na PNC-27 na-ebute pores na-eme ka mkpụrụ ndụ cancer dịkwuo elu na Gemzar, na-enye ohere ka ọtụtụ Gemzar lekwasị anya na mkpụrụ ndụ kansa [1].
Ọrịa Ovarian:
Na ahịrị sel cancer ovarian SKOV-3 na OVCAR-3, a na-egosipụta protein HDM-2 nke ukwuu na akpụkpọ ahụ cell.PNC-27 na-ejikọta HDM-2 na akpụkpọ ahụ cell, na-eduga na necrosis cell ngwa ngwa. N'ụzọ dị iche, n'ahịrị cell HUVEC na-agbanweghị agbanwe, a hụghị njikọ na cytotoxicity nke PNC-27 n'ihi ntakịrị okwu HDM-2 [1]..
Ọrịa cancer colon:
PNC-27 na-ahọrọ gbuo mkpụrụ ndụ kansa eriri afọ. N'ime ahịrị mkpụrụ ndụ cancer nke eriri afọ isii, PNC-27 jikọtara ya na akpụkpọ ahụ HDM-2 wee kpatara ọnwụ cell (necrosis tumor cell, ntọhapụ LDH dị elu, protein V na cysteine 3 negativity) naanị na mkpụrụ ndụ kansa. Na vivo, PNC-27 na-akpata necrosis nke nodules tumor mana ọ naghị emetụta anụ ahụ nkịtị [1].
3. Mma mgbochi tumor arụmọrụ
Njide na Doxil:
Achọpụtara na peptide PNC27, dị ka ligand ezubere iche, nwere ike ịkwalite nrụpụta mgbochi tumor Doxil na mkpụrụ ndụ kansa HDM2 dị mma. A na-etinye peptide PNC27 dị iche iche na Doxil, na cytometry na-asọpụta na nyocha nke confocal ka emere na C26 colon cancer (HDM2-positive) na B16F0 melanoma (HDM2-negative). Nsonaazụ gosiri na PNC27-Doxil gosipụtara nnabata cellular dị ịrịba ama na cytotoxicity na sel C26, ebe achọpụtaghị nsonaazụ ndị a na sel B16F0. Dịka ọmụmaatụ, PNC27-Doxil (100 PNC27 peptide) mụbara uru ọgwụgwọ Doxil n'ebughị ụzọ mebie biodistribution na etuto C26 [4].
4. Ọgwụgwọ synergistic nke ọrịa cancer ovarian na paclitaxel
A na-eji Paclitaxel eme ihe n'ọtụtụ ebe n'ịgwọ ọrịa ọrịa gynecological, ma ọ na-elekwasị anya na mkpụrụ ndụ tumor na usoro M nke cell cell, na mkpụrụ ndụ n'ime usoro ndị ọzọ na-adị ndụ ma nwee ike iduga nlọghachi azụ. Achọpụtara mkpụrụ ndụ cancer ID8 nke ovarian nke ekpughere na paclitaxel iji gosipụta mmụba nke MDM-2 na mmụba na-enwe mmetụta na PNC-27. Mmetụta cytotoxic nke PNC-27 na-adabere na njide ya na MDM-2, na igbochi MDM-2 na-egbochi mmetụta igbu nke PNC-27. Ihe oyiyi heterodrug nke nchịkọta dose ahụ bụ mmekọrịta, na-atụ aro mmetụta mmekọrịta n'etiti PNC-27 na paclitaxel [5] . N'ụdị intraperitoneal nke ọrịa cancer ovarian (ID8), mgbakwunye PNC-27 na nchịkwa paclitaxel kwa izu na-ebelata oke etuto ahụ. Data ndị a na-egosipụta mmetụta synergistic n'etiti PNC-27 na paclitaxel, yana PNC-27 na-ezubere paclitaxel na-anwụ anwụ cell na imeziwanye mmetụta antitumor ya.
5. Ọgwụgwọ nke isi epithelial ovarian cancer
Otu nnyocha ewepụtala omenala ndị bụ isi nke mkpụrụ ndụ kansa epithelial ovarian dịpụrụ adịpụ site n'aka ndị ọrịa nwere cystadenocarcinoma ovarian ovarian a chọpụtara ọhụrụ. Otu n'ime ha sitere na cystadenocarcinoma mucinous na nke ọzọ sitere na papillary plasmacytoid carcinoma dị elu. A na-enyocha ịdị irè ọgwụgwọ nke PNC-27 nke ọma site na nlele microscopic qualitative light na MTT cell proliferation assay yana nha nke lactate dehydrogenase (LDH). Nsonaazụ gosiri na PNC-27 gbochiri uto mkpụrụ ndụ kansa kansa mmadụ nke dịpụrụ adịpụ site na carcinomas epithelial ovarian abụọ n'ụzọ dabere na dose ma bụrụ cytotoxic nye ha. Njikwa peptide PNC-29 enweghị mmetụta na mkpụrụ ndụ kansa nke mbụ. Na mgbakwunye, PNC-27 bụkwa cytotoxic maka ahịrị mkpụrụ ndụ kansa ovarian nke mmadụ na-egbochi ogologo oge yana chemotherapy ..
Na nchịkọta, PNC-27, dị ka akwụkwọ akụkọ anticancer peptide, na-egosi ike dị ukwuu maka itinye n'ọrụ n'ọtụtụ ọgwụgwọ ọrịa cancer. N'ihe gbasara ọrịa leukemia, PNC-27 gosipụtara mmetụta igbu ọchụ na nnukwu ọrịa leukemia myeloid (dịka, U937, OCI-AML3, na ahịrị cell HL60) na p53-deficient K562 cell, wee nweta mmetụta antitumor dị oke mma site n'ime ka cell necrosis na lactate dehydrogenase hapụ. N'ịgwọ ọrịa cancer ovarian, nchikota nke PNC-27 na paclitaxel gosipụtara mmetụta synergistic, nke nwere ike igbochi uto tumor ma ka na-egbu egbu megide mkpụrụ ndụ na-eguzogide chemotherapy. Na mgbakwunye, nchikota nke PNC-27 na liposomal ọgwụ (dịka Doxil) dị ka a ezubere iche ligand nwere ike welie kpọmkwem nnyefe na mgbochi tumor irè nke ọgwụ na HDM2-positive tumor cell. Mmetụta mgbochi ya na sel progenitor nke mbụ epithelial ovarian cancer na-akwado uru ntụgharị ụlọ ọgwụ. Ka ọ dị ugbu a, PNC-27 abanyela n'ọgba aghara ụlọ ọgwụ nke Mbụ, yana a chọkwuru ọmụmụ ụlọ ọgwụ iji kwado nchekwa ya na ịdị ogologo oge, iji kwalite ya dị ka ihe ngwọta ọhụrụ maka ọgwụgwọ ọrịa kansa.
Banyere Onye dere ya
Ihe niile a kpọtụrụ aha n'elu bụ Cocer Peptides na-enyocha, dezie ma chịkọta ya.
Onye ode akwụkwọ akụkọ sayensị
Sarafraz-Yazdi E bụ onye nyocha metụtara ọtụtụ òtù, gụnyere NomoCan, New York Blood Center, SUNY Downstate Health Sciences University, na New York Harbor VA Med Ctr. Njikọ ndị a na-egosipụta ntinye aka ya na nyocha dị iche iche na gburugburu ahụike.
Mmasị nyocha ya gbasara ụdị isiokwu dị iche iche dị ka Oncology, Technology Laboratory Technology, Pharmacology & Pharmacy, Biochemistry & Molecular Biology, na Research & Experimental Medicine. Ọrụ ya na ngalaba ndị a na-egosipụta nnukwu nka na ntinye aka ya n'ịkwalite ihe ọmụma na mpaghara ndị a dị mkpa nke sayensị ahụike na nyocha. A na-edepụta aha n'akwụkwọ ntụaka [3].
