Y HOC VIET NAM THANG 4 - SO 2/2015 Shah, M.I., A. Chantal Caviness, and D.R.
Mendez (2013). Prospective Pilot Derivation of a Decision Tool for Children at Low Risk for Testicular Torsion. Academic Emergency Medicine, 20(3), pp. 271-278.
Alyami F and T Wheian (2013). Incarcerated inguinal hernia in infancy associated with testicular infarction: Case report and review of the literature. Canadian Urological Association
Journal, 7(5-6), pp. E367.
Singal AK et al (2013). Undescended testis and torsion: is the risk understated? Archives of disease in childhood, 98(1), pp. 77-79.
Munden MM et al (2013). Intermittent testicular torsion in the pediatric patient:
sonographic indicators of a difficult diagnoas. AJR Am J Roentgenol, 201(4), pp 912-918.
NGHIEN CITU TAC DUNG UC CHE UNG THIT C O A T 6 I DEN TREN CHUOT MANG KHOI UNG THU GAN NGU'O'I
T 6 M TAT
Mtfc tiiu: Nghien cdu nay dUde thyc hien de danh gia hi?u qua chong ung thiT cua tdi den tren chupt mang khoi te bao ung thu gan ngu'di. Phu'dng phap: Chugt thieu hyt mien djch mang khoi ung thU gan ngu'di dude dieu tri bang uong dung dich bpt toi den vdi lieu 1 g hOciclO g/kg can nang moi ngay. Ket qu^: Ket qua nghien cdu cho thay, d ca hai mdc lieu dieu tri toi den deu co tae dyng de che sy phat trien khdi ung tJiU va keo dai thdi gian song va ti le chupt song ro ret so vdi nhdm ehuhg (p<0,05). Ket luan:
Nghien ciru nay cho thay tren md hinh chupt mang khdi ung thu" gan ngudi, tdi den cd tae dung dc che khoi u phat trien va keo dai thdi gian song eiia chupt du'dc dieu tri.
TO'khda: toi den, chupt thieu hut mien djch, ung thy gan
SUMMARY
STUDY THE ANTI-CANCER OF BLACK GARLIC ON MICE BEARING HUMAN
HEPATOCARCINOMA TUMORS Aims: The present study was conucted to investigate the anticancer effect of black garlic on nude mice bearing human liver cancer tumors.
Methods: The nude mice bearing human liver tumors were treated with doses of I g or 10 g/kg body weight, by drink daily of black garlic powder. Results; The results shown that with two difference dose of the
* Benh vien Y hoc Co truyen Quan dpi
** Hoc vien Quan y
Chju trach nhiem chinh: Ho Anh Son Email: [email protected] Dt: 0978437229 Ngay nh|n bai: 28/2/2015
Ngay phan bi^n khoa hoc: 10/3/2015 Ngay duyet bai: 16/3/2015
Ph^m Xuan Phong*, Ho Anh Scrn**
black garlic powder, they significantly inhibited the cancer tumor growing and prolong alive time and rate of alive nude mice beanng human liver tumor^
compare to control group (p<0.05). Conclusionsi This study indicated on nude mice beanng human liver tumors, the black garlic powder inhibited the cancer tumor growing and prolong alive time.
Keywords: black garlic, nude mice, hepatocellular carcinoma
I. OAT V X N O E
Trong thanh phan hda hpc ciia tdi den sau khi len men ham lu'dng mot so acid amin ty do tang ro ret so vdi tru'dc khi len men nhu": Add aspartic, threonin, Methiolin, Arginin...Dac biet la cac thanh phan goc hull cd cd chu^ sulftia co hoat tinh manh me, cd kha nang chong lai nliieu benh tat, trong dd cd kha nang khang ung thi/.
Cac nghien ciTu gan day eiia chiing tdi cho thay, tdi den cd hoat tinh chong mot so dong te bao ung thu' nhu' dai trang, bao ve ed quan tao mau, dong thdi tang cu'dng hoat dpng ciia he thong mien djch.
Tren the gidl, nghien cdu ciia Sasaki (2007) khi tiem dich chiet tdi den vao chupt thieu hyt mien djch mang te bao ung t h d ngu'di thi te bao ung t h d bien mat hoac giam di 50% trong kill nhdm chdng te bao ung thu" tang len ro ret.
Ngoai ra, nghien culj tu'dng t y tren nhuhg khi Sasald den hanh vdi tdi thu'dng thi hieu qua cal thien cua ca hai nhdm deu khong the nhdtdi den [5],
Trong nghien cdu nay, chung toi danh gia tae dyng khang ung thu* ciia tdi den tren m5 hinh chudt thieu hyt mien djch mang khoi ung thu" gan.
Y HOC VIET NAM THANG 4 - SO 2/2015 II. DO\ T U O N G VA PHUONG PHAP NGHIEN CCTU
2 . 1 . O o i t u ' d n g :
- Chupt thieu hut mien djch (nude mice) (chupt nude) dong BALB/c, 4-6 tuan tuoi, dMc nhap khau t d cong ty Sigma, Hoa Ky.
- Te bao ung thu' gan ngu'di Hep 38 (ATCC, Hoa Ky).
2 . 2 . T h i e t b i v a h o a c h a t :
- Mau bpt phun say cao kho chira 5 0 % tdi den (TD)^dat TCCS (sd 16 010313) do Trung tam nghien cdu dng dung san xuat thuoc - Hpc vien Quan y cung cap.
- Moi trudng nuoi cay te bao: moi trudng nuoi cay te bao DMEM, huyet thanh bao thai be (FBS), dung djch penicillin/ streptomycin, dung djch PBS, dung djch Trypsin-EDTA (ATCC, Hoa Ky),
2.3. Phu'dng p h a p n g h i e n cili'u 2.3.1. Nuoi cay va tang sinh tebao:
- Nuoi cay te bao ung t h d gan ngu'di ngu'di dong Hep 3B, du'dc nuoi cay trong moi tru'dng DMEM bo sung 10% FBS, 1 % penicillin va streptomycin, Te bao du'dc nuoi cay, tang sinh trong chai cd dien tich day chat 75 c m ^ dat trong t i i vd trung, duy tri nhiet dp 37°C va COj 5%.
- Thay moi tru'dng nuoi cay 3 ngay/lan. Khi te bao dat m$t dp 8 0 % dien ti'ch be mSt chai, tach khdi chai nuoi bang Trypsin EDTA 0,05% va cay chuyen sang chai nuoi cay mdi. Khi sd lu'dng te bao dii Idn, thu hoach te bao va dem so lu'dng te bao thu dddc, dieu chinh mat dp te bao dat mat d o l O ' t e b a o / m l .
2.3.2. Ghep te bao ung thu" gan ngu'cff Hep 3B ten chupt nude
- Chupt nude dddc co dinh va tiem 0,1 ml dung djch chiia te bao mat do 1 0 ' te bao/ml vao du'di da dill phai. Qua trinh thao tae dddc thyc hien
trong dieu kien v6 triing tuyet doi.
2.3.3. Theo doi va xac dinh sit hinh thanh khdi ung thu" tren chugt
Khdi u du'dc danh gia theo doi sy phat trien tai vj tri tiem (dCii phai) 2 lan moi tuan, bang quan sat, sd nan va do ki'eh thu'de khdi u bang thu'de chinh xac NSK.
+ Ki'eh thu'de khdi u; khdi u du'dc do theo hai kich thu'de dai x rdng bang thu'de ehi'nh xac NSK (Nhat Ban), 2 lan/tuan.
ki'eh thUde u du'dc tinh theo cong thdc: V - D X R^ X 0,5^
V: the tich khoi u; D: chieu dai khoi u; R:
chieu rpng khoi u
2.4. Phan n h o m va each suf d u n g t o i d e n Chupt nude du'dc ghep te bao ung t h d gan ngu'di Hep 3B vdi lieu 10^ te bao/con, chupt dddc ngau nhien chia thanh cac nhdm va uong vien nang tdi den nhd sau:
- Nhdm chdng: 10 chupt nude, hang ngay 6\i^z cho uong nu'dc cat tu'dng img vdi the ti'ch 0,lml/10 g the trpng, lien tyc trpng 4 tuan.
- Nhdm dieu tri 1: 10 chuot nude, hang ngay du'dc cho udng nu'dc hda tan bpt eiia vien nang tdi den vdi lieu tu'dng dng I g / k g the trpng/ngay, du'dc pha vdi the tich 0,lml/10 g the trpng, Chupt dddc udng lien tuc trong 4 tuan.
- Nhdm diieu trj 2: 10 chupt nude, hang ngay du'dc cho uong ndde hda tan bpt cua vien nang tdi den vdi lieu tu'dng dng lOg/kg the trong/ngay, dddc pha vdi the tich 0,lml/10 g the trpng. Chupt du'dc udng lien tuc trong 4 tuan.
Theo doi toe dp phat trien khoi u, thdi gian song trung binh. Thi nghiem dtrng d thdi diem sau khi bat dau dieu trj bang toi den 3 thang.
III.
K I T Q\JA3 . 1 . K i c h thu'de k h o i u g a n t r § n cac n h o m c h u o t
Chung (1) Dieu trj 1
(2) Dieu tri 2
(3) P
Ngay 0 78,3 75,2 106,5
>0,05 Ngay
7 118,5 163,6 131,8
>0,05 Ngay
14 215,4 270,0 241,2
>0,05 Ngay
21 312,8 353,8 304,9
>0,05 Ngay
35 344,0 450,1 360,0
>0,05 Ngay
42 507,0 484,2 443,2
>0,05 Ngay
49 609,3 683,5 542,0
Pl3<0,05 Ngay
56 907,8 787,7 610,8 Pl-3
<0,05 Ngay
63 1203,5 883,9 708,6
Pl-2,3
<0,05
Kit qua cho thay khoi u cua cac nhom chugt van tang dan deu theo thdi gian, den ngay 63 thi co 1 chugt nhdm chi/iig chit Qua trinh do kich thddc khdi u du'dc dung lai. Trong giai doan dau cua dieu tri, kich thude trung binh khoi ung thw aja cac nhdm chupt khong co sd khac biet cd ban.Y HOC VIET NAM THANG 4 - 5 6 2/2015
Bieu dd 3,1, Dien bien kich thifdc khoi u gan Hep3B
Nhdm dieu tri 1, vdi lieu tdl den Ig/kg an nang, cho thay stfkhac blet cd y nghia thong ke re Uch thude trung binh khoi u so vdi nhdm chung vao lan do cuol ciing (ngay 63).
Nhdm dieu b-i2, cd kich thude trung binh khoi u nhd hdn nhdm chiing mot each cd y nghia thing ke by ngay 56. Dong thdi, tai thdi diem nay kich thude trung binh khoi u cua nhdm dieu trj 2 cung nhd hdn dang keso vdi nhdm dieu tri 1 (p<0,05).
3.2. Ti le song, chet cua cac nhom chuot Bieu 00 3.2. Ti le chupt song/chet theo thdi gian
Sau khi hinh thanh khoi u, chuot dude uong tdl den trong vdng 1 thang. Tai thdi diem 63 ngay, da xuat hien chugt mang u ehet tai tat ca cac nhdm. Tuy nhien, toe dp chupt ehet nhanh hdn d nham ehuhg. Tai thdi diem kit thuc thi nghiem (ngay 90), so lu'dng chuot eon song d cae nhdm chung, dieu tii 1 va dieu hi 2 lan lifdt ia 30%, 40% va 60%. Si/khie blet niy ehua ed y nghia thong ke.
3.3. Thcri gian song trung binh cua cac nhom chuot
Bang 3.2. Th6i gian song trung binh ciia cac nhom chuot den th6i diem ket thuc thi nghiem Thdi gian song
TB
Chu'ng f>reu tri 1 _(2i:
Sieu tri 2 J 3 L
83,7
Thdi gian song trung binh cua chupt mang khdi ung thu'gan dUde dieu tn bang tdl den cho thay co
xu bu'dng dai hdn nhdm khong du'dc dieu tn. Tuy nhien sir khae blet nay chu'a cd y nghia thong ke.
Y HOC VIET NAM THANG 4 - SO 2/2015 IV. BAN L U A N
Ket qua nghien cifu ciia chiing tdi cho thay, chupt nude mang khoi ung thU gan ngu'di du'dc udng tdi den de dieu tri vdi lieu 10 g/kg/ngay keo dai mot thang cd tae dung kim ham su' phat trien kich thu'de khoi ung thu". Dong thdi, chupt mang u du'dc uong tdi den cd ti le song cao hdn va thdi gran song dai hdn so vdi nhom chdng.
Cac nghien cdu cho thay, trong tdi cd nhieu thanh phan khac nhau nhu' eac hdp chat lu'u huynh hud cd va seien cd tae dung de che sy tang sinh cua te bao ung thu", dieu chinh chu \^
te bao va gay apoptosis2, 3, nhieu nghien cyu thay-hoat chat chinh cua tdi ed the gay ehet te bao theo chu'dng trinh (apoptosis) tren dong te bao ung thu" gan Hep 3B bdi sd dieu hda cac goc ty do thong qua cac gay ton thu'dng mang ty the, giam bpc Ip cac gen chong apoptosis nhu"
Bcl-2 va Bd-xl. Dong thdi, djch chiet tdi gay tang bieu 16 cac gen gay ehet theo chu'dng trinh (apoptosis) nhy eapase 3, capase 8 va capase 9, tiir dd thuc day te bao ung thd gan chet [3-5].
Nghien cuti tu'dng ty tren dong ung thu" te bao gan Hep G2, cac tae gia cho thay kha nang kim ham sy phat trien dong te bao nay, cac bang chiitig cho thay nong dp protein p53 npi bao tang dang ke trong cac te bao du'dc dieu trj bSng Allicin tif tdi va gay giam nong dp Bcl-2.
Ngu'dc lai, Alllcln lam tang bpc 16 AMPK/fsC2 va con dddng tin hieu Beelin-1 trong dong te bao ung thy bieu md gan Hep G2 thuc day qua trinh chet te bao 7.
Tren thyc nghiem, S-aliyleystelne (SAC) cd tae dung dc che sd phat trien ciia dong ung thd phdi idiong te bao nhd NSCLC A-549. SAC cho thay kha nang de che ddng te bao nay thong qua lie che sd hoat hda cae phan td mTOR, NF- KB, va eyeiin DI [7]. Dong thdi, SAC con de che sy di can ciia ddng ung thd phoi khong te bao nhd tren chupt mang khoi ung thd nay, Cac tae gia cung phat hien cd che chong ung thu' ciia tdi tren ung thd phoi cOng tddng ty nhd cae ddng ung thd khac 4,
Nghien cdu ciia Sasaki (2007) khi tiem djch chiet tb\ den vao chuot thieu hut mien djch mang te bao ung thd ngddi thi te bao ung thd bien mat hoac giam di 50% trong khi nhdm ehuhg te bao ung thd tSng len ro ret. Ngoai ra, nghien
eii\j tu'dng ty tren nhu'ng khi Sasaki tien hanh vdi tdi thu'dng thi hieu qua cai thien ciia ca hai nhdm deu khong the nhu'tdi den [ 5 ] .
V. KET LUAN
Ket qua nghien ciru tae dyng khang ung thu' ciia tdi den tren chupt thieu hyt miln djch mang khdi ung thu' gan ngu'di vdi lieu 10 g/kg/ngay hang ngay keo dai mot thang cd tae dung kim ham sy phat trien khdi ung thU ro ret so vdi nhdm chdng (p<0,05). Dong thdi, chupt mang khdi ung thu' gan ngu'di dddc uong tdi den cd ti le song nhieu hdn va thdi gian song dai hdn ro ret so vdi nhom chdng khong dieu trj (p<0,05), TAI Ll|U THAM KHAO
1 . Ho Anh Stfn, Vu Binh Du'dng (2014). "Nghien ciru tae dung ire che te bao ung thU dai trang ciia djch chiet toi den va tae S-allyl-L-cystein phan lap tdtoi den", Tap chi dupe hpc, 460,27-31.
2. Nian H, Deiage B, Ho E, Dashwood RH (2009). "Modulation of histone deacetylase activity by dietary isothiocyanates and allyl sulfides: studies with sulforaphane and garlic organosulfur compounds". Environ Mol Mutagen., 50(3), pp. 213-21.
3. Stan SD, Singh SV (2009). Transcriptional repression and inhibition of nuclear translocation of androgen receptor by diallyl trisulfide in human prostate cancer cells", Clin Cancer Res., 15(15), pp. 4895-903.
4. Lee BC, Park BH, Kim SY, Lee YJ (2011).
"Role of Bim in diallyl trisulfide-lndueed cytotoxicity in human cancer cells", J Cell Biochem., 112 (1),118-127.
5. Sasaki J., Lu C, Machiya E, Tanahashi M, Hamada K, (2007). Processed black garlic (Allium sativum) extracts enhance anti-tumor potency against mouse tumors. Med/c//?a/ and Aromatic Plan Science and Biotechnology, 1 (2), 278-281.
6. Mousa AS, Mousa SA (2005). "Anti- angiogenesis efficacy of the garlic ingredient alliin and antioxidants: role of nitric oxide and p53", A'i//rCSncer;53:104-10.
7. Tang FY, Chiang EP, Pal MH (2010).
Consumption of S-Allylcysteine Inhibits the Growth of Human Non-Small-Cell Lung Carcinoma in a Mouse Xenograft Model", J Agiic Food Ch&n, 9(24), 1156-1164.
