한국인 신이식 수혜자에서 transforming growth factor-β1 및 vascular endothelial growth factor 유전자의 단일염기다형성이 만성 이식신 신병증과 이식신 생존율에 미치는 영향

조지형 ( Ji Hyung Cho ),류혜명 ( Hye Myung Ryu ),진미경 ( Mi Kyung Jin ),전주현 ( Joo Hyun Chun ),현승혜 ( Seung Hyea Hyun ),최지영 ( Ji Young Choi ),허인경 ( In Kyong Hur ),이은영 ( Eun Young Lee ),박선희 ( Sun Hee Park ),김용림 대한신장학회 2008 Kidney Research and Clinical Practice Vol.27 No.4

목적: 염증반응과 섬유화에 관여하는 Transforming growth factor-β1 (TGF-β1)와 이식신에 대한 cytoprotection에 관여하는 vascular endothelial growth factor (VEGF)는 만성 이식신 신병증 (CAN)의 발생과 연관이 있을 것으로 추측되어 왔다. 이에 저자들은 한국인 신이식 수혜자를 대상으로 TGF-β1 및 VEGF 유전자 SNP과 이식신 생존율 및 CAN과의 상관관계에 대해 조사하였다. 방법: 경북대학교병원에서 신이식을 시행한 환자 중 유전자 분석에 동의한 221명과 건강한 대조군 148명을 대상으로 TGF-β1 유전자의 C-509T 및 T869C, VEGF 유전자에 있는 C-2578A, C405G의 유전자형을 분석하였다. 신이식 후 CAN이나 만성 calcineurin inhibitor 신독성으로 진단된 경우를 신병증군 (n=21)으로 그렇지 않은 경우를 정상 이식군 (n=200)으로 분류하였다. 결과: 신이식 환자군과 정상 대조군에서 확인된 TGF-β1 (C-509T, T869C) 및 VEGF 유전자의 SNP (C- 2578A, C405G)의 유전자형의 빈도는 Hardy-Weinberg 평형에 따른 기대빈도와 유의한 차이가 없었고, 신이식 환자군과 정상 대조군에 있어 TGF-β1 및 VEGF 유전자 SNP의 유전자형과 대립형질의 빈도에는 유의한 차이가 없었다. TGF-β1의 C-509T와 T869C 및 VEGF의 C-2578A와 C405G는 강한 유전적 상관 관계를 보였고 (D`=0.78-0.98), 두 군 간 각각의 일배체형 간의 빈도 차이는 없었다. 전체 신이식 환자를 대상으로 TGF-β1 및 VEGF 유전자 SNP의 유전자형에 따라 두 군으로 나누어 Kaplan-Meier 생존분석을 시행한 결과 이식신 생존율은 유의한 차이가 없었고, 저농도 혹은 고농도의 cytokine 생산과 관련된 유전자형에 따른 이식신 생존율도 각 cytokine 모두 유사하였다. 결론: 본 연구에서 조사한 TGF-β1 및 VEGF 유전자 SNP은 한국인 신이식 수혜자에서 이식신 생존 또는 만성 이식신 신병증 발생 여부에 따라 차이를 보이지 않았다. Purpose: Transforming growth factor-β1 (TGF-β1) has been associated with the promotion of renal allograft interstitial fibrosis and thereby chronic allograft nephropathy (CAN). Vascular endothelial growth factor (VEGF) has been shown to contribute to cytoprotection of the graft after kidney transplantation. We investigated the influence of single nucleotide polymorphisms (SNPs) of the TGF-β1 (C-509T and T869C) and the VEGF gene (C-2578A and C405G) on graft survival and the development of CAN. Methods: Genotyping was carried out using a real-time polymerase chain reaction which was performed on the LightCycler480 in 221 Korean renal transplant recipients and 148 healthy controls. According to the presence of CAN or chronic calcineurin inhibitor nephrotoxicity, the recipients were separated into the CAN (n=21) and the No CAN (n=200) groups. Results: The genotype frequencies of the SNPs were in Hardy-Weinberg equilibrium. The distributions of genotypes and alleles did not differ between recipients and controls. No significant differences were observed in the genotype distributions and allele frequencies between the CAN and the No CAN groups. The frequencies of haplotypes were not significantly different between the two groups, either. There were no statistically significant effects of TGF-β1 and VEGF gene polymorphisms on graft survival. Conclusion: This study did not show any statistically significant effects of four selected SNPs of the TGF-β1 and the VEGF genes on the development of CAN and graft survival in Korean renal transplant recipients.

Individual Variation in Growth Factor Concentrations in Platelet-rich Plasma and Its Influence on Human Mesenchymal Stem Cells

조희순,송인환,박소영,성민철,안면환,송경은 대한진단검사의학회 2011 Annals of Laboratory Medicine Vol.31 No.3

Background: The objective of this study was to explore whether individual variations in the concentration of growth factors (GFs) influence the biologic effects of platelet-rich plasma (PRP) on human mesenchymal stem cells (HMSCs). Methods: The concentrations of 7 representative GFs in activated PRP (aPRP) were measured using ELISA. The effects of PRP on the proliferation and alkaline phosphatase (ALP) activity of HMSCs were examined using several concentrations of aPRP from 3 donors; the relationships between the GF levels and these biologic effects were then evaluated using 10% aPRP from 5 subgroups derived from 39 total donors. HMSCs were cultured in DMEM with the addition of aPRP for 4 or 12 days; then, DNA content and ALP activity were measured. Results: The quantity of DNA increased significantly at a 10% concentration of aPRP, but the ALP activity was suppressed at this concentration of aPRP. The GF concentrations varied among donors, and 5 subgroups of characteristic GF release patterns were identified via cluster analysis. DNA levels differed significantly between groups and tended to be higher in groups with higher concentrations of transforming growth factor-beta1 (TGF-β1) and platelet-derived growth factors (PDGFs). DNA quantity was positively correlated with TGF-β1 concentration, and was negatively correlated with donor age. ALP activity was negatively correlated with PDGF-BB concentration. Conclusions: The varying GF concentrations may result in different biologic effects; thus, individual differences in GF levels should be considered for reliable interpretation of the biologic functions and standardized application of PRP. Background: The objective of this study was to explore whether individual variations in the concentration of growth factors (GFs) influence the biologic effects of platelet-rich plasma (PRP) on human mesenchymal stem cells (HMSCs). Methods: The concentrations of 7 representative GFs in activated PRP (aPRP) were measured using ELISA. The effects of PRP on the proliferation and alkaline phosphatase (ALP) activity of HMSCs were examined using several concentrations of aPRP from 3 donors; the relationships between the GF levels and these biologic effects were then evaluated using 10% aPRP from 5 subgroups derived from 39 total donors. HMSCs were cultured in DMEM with the addition of aPRP for 4 or 12 days; then, DNA content and ALP activity were measured. Results: The quantity of DNA increased significantly at a 10% concentration of aPRP, but the ALP activity was suppressed at this concentration of aPRP. The GF concentrations varied among donors, and 5 subgroups of characteristic GF release patterns were identified via cluster analysis. DNA levels differed significantly between groups and tended to be higher in groups with higher concentrations of transforming growth factor-beta1 (TGF-β1) and platelet-derived growth factors (PDGFs). DNA quantity was positively correlated with TGF-β1 concentration, and was negatively correlated with donor age. ALP activity was negatively correlated with PDGF-BB concentration. Conclusions: The varying GF concentrations may result in different biologic effects; thus, individual differences in GF levels should be considered for reliable interpretation of the biologic functions and standardized application of PRP.

탄소봉을 이용한 종합가시광선이 흰쥐의 피부창상 치유에 미치는 영향

서일복 ( Il Bok Seo ),송재철 ( Jae Chul Song ),경기도 ( Jong Soo Lee ),성남시 ( Seok Hee Chung ),분당구 ( Sung Soo Kim ) 한방재활의학과학회 2002 한방재활의학과학회지 Vol.12 No.2

Objectives : Our purpose was to evaluate the efficacy of Full Spectrum Visible Ray of carbon electrodes No. 3000 and No. 3002, No. 3001 and No. 4008 in the healing of full-thickness excision wound. Methods : We used Sprague-Dawley rats of 8 weeks aged. They were divided thre e groups, one control group and two experimental groups. Full-thickness excision wound were made on the back of the all rats of each group. Full Spectrum Visible Ray of carbon electrodes, No. 3000 and No. 3002 were radiated to rats of one experimental group in 15 minutes a day for 2 weeks. Full Spectrum Visible Ray of carbon electrodes, No. 3001 and No. 4008 were radiated to rats of the other experimental group in 15 minutes a day for 2 weeks. The exicision wounds were examined in tensely on the 1st, 2nd, 4th, 7th, 14th day after exicision. Morphological changes were examined in hematoxylin-eosin staining and azan staining. Epidermal growth factor, transforming growth factor β1, transforming growth factorβ3 were examined in immunohistochemical staining. Results :1. Full Spectrum Visible Ray of No. 3000 and 3002 carbon electrodes have effects to accelerate wound healing process. 2. Full Spectrum Visible Ray of No. 3001 and 4008 carbon electrodes have anti-inflammatory effects. 3. Transforming growth factor β1 and β3 have competitive inhibition actions. Conclusions : These findings suggest that Full Spectrum Visible Ray of No. 3000 and 3002 carbon electrodes have accelerating effects on full-thickness exicision wound healing, and that Full Spectrum Visible Ray of No. 3001 and 4008 carbon electrodes have anti-inflammatory effects.

Leukocyte-Poor Platelet-Rich Plasma-Derived Growth Factors Enhance Human Fibroblast Proliferation In Vitro

노규철,Xiao Ning Liu,Zhong Zhuan,양철중,김용태,이근우,최경호,김경옥 대한정형외과학회 2018 Clinics in Orthopedic Surgery Vol.10 No.2

Background: Leukocyte-poor platelet-rich plasma (LP-PRP) from peripheral blood is currently used as a concentrated source of growth factors to stimulate repair at sites of soft tissue injury. Fibroblasts are primary mediators of wound healing. Thus, we aimed to assess the positive effect of LP-PRP on human fibroblast proliferation in vitro . Methods: LP-PRP was prepared from 49 donors. The fibroblasts were seeded, and at 24 hours after seeding, 1 × 107/10 μL LP-PRP was added once to each well. The cells were harvested 10 times during study period at our planned points, and we examined cell proliferation using the water-soluble tetrazolium salt-1 assay. We collected the supernatants and measured the amount of growth factors such as platelet-derived growth factor (PDGF)-AB/BB, insulin-like growth factor-1 (IGF-1), transforming growth factor-β1 (TGF-β1), and vascular endothelial growth factor (VEGF), which are known to be involved in wound healing processes, by multiplex assay. Results: Human fibroblasts treated with LP-PRP showed a significant increase in proliferation when compared to untreated controls (p < 0.001 at days 4, 6, and 8). Multiplex cytokine assays revealed various secretion patterns. PDGF-AB/BB appeared at early time points and peaked before fibroblast proliferation. IGF-1 and TGF-β1 secretion gradually increased and peaked on days 4 and 6 post-treatment. The early VEGF concentration was lower than the concentration of other growth factors but increased along with cell proliferation. Conclusions: Platelets in LP-PRP release growth factors such as PDGF, IGF-1, TGF-β1 and VEGF, and these growth factors have a promoting effect for human fibroblast proliferation, one of the important mediators of wound healing. These results suggest that growth factors derived from LP-PRP enhance the proliferation of human fibroblast.

신세포암에서 Transforming Growth Factor-β1과 수용기 Ⅰ, Ⅱ, Ⅲ의 발현 변화

강상수,민경대,정승일,김세연,오봉렬,류수방,박양일 全南大醫大 2000 전남의대학술지 Vol.36 No.4

암 환자의 혈장 Transforming Growth Factor-β1 농도

박병규,하우송,이시은,이수진,박순태,박찬후,전지현,장정순 THE KOREAN SOCIETY FOR BIOMEDICAL LABORATORY SCINE 1999 Journal of biomedical laboratory sciences Vol.5 No.2

한국인의 대표적인 성인 고형 종양인 위암, 간암, 유방암과 소아 백혈병 및 2종의 소아 고형 종양 환자로부터 혈장 transforming growth factor-ß1 (TGF-ß1) 농도를 sandwich ELISA 분석법을 이용해 측정함으로써 TGF-ß1을 이 질환들에 대한 새로운 종양표지자 (tumor marker)로 사용할 수 있는지 검토하였다. 또한 연령 및 성별에 따른 혈장 TGF-ß1 농도의 정상치를 조사하였다. 신생아에서 70대까지 혈장 TGF-ß1 농도의 차이는 없었고 남녀간의 차이도 없었다. 위암 환자의 혈장TCF-ß1 농도는 16.0±6.8 ng/ml (평균 ±표준편차)로 정상 대조군의 TGF-ß1 농도 (8.3 ±5.0 ng/ml) 보다 유의하게 높았으나 간암, 유방암 환자의 혈장 TGF-ß1 농도는 대조군과 차이가 없었다. 그리고 위암 환자 16명, 간암 환자 8명, 유방암 환자 7명 중 각각 7명 (43.7%), 1명 (12.5%), 1명 (14.3%)에서만 혈장 TGF-ß1 농도가 증가되었다. 5명의 소아 백혈병 환자에서는 관해 (remission) 여부와 상관없이 혈장 TGF-ßl 농도가 모두 정상 범위에 있었으나 2명의 소아 고형암 환자에서는 종양 절제 전에는 혈장TGF-ß1 농도가 높았다가 절제 후 정상으로 떨어졌다. 결론적으로 1)정상인의 혈장 TGF-ßl 농도는 연령 및 성별에 따른 차이가 없다는 것을 알 수 있었고, 2)성인 고형암인 위암, 간암, 유방암에서는 낮은 민감도로 인해 TGF-ß1을 진단을 위한 선별 검사로 이용하기에는 부적절한 것으로 판단되었으며, 3) 정상 대조군보다 혈장 TGF-ß1 농도가 높았던 위암 환자와 종양 절제 전후로 혈장 TGF-ß1 농도가 민감하게 변했던 소아 고형 암 환자에 대해서는 향후 표본 수를 늘려 부가적인 연구를 해 야 할 것으로 사료된다. To evaluate the usefulness of transforming growth factor-ß1 (TGF-ß1)as a new tumor marker, we determined the plasma TGF-ß1 levels using sandwich ELISA assay in cancer patients. Patients with three most common adult cancers in Korea (stomach, liver and breast cancer) and children's cancers (leukemia and two kinds of solid tumor) were enrolled for the study. Furthermore, 39 individuals were subjected to age and sex-stratified plasma TGF-ß1 analysis. No statistical difference was demonstrated with respect to age or sex. The mean plasma TGF-ß1 level (16.0 ng/ml) of stomach cancer patients was significantly higher than that (8.3ng/ml) of controls. However, there was no difference among the mean plasma TGF-ß1 levels of liver, breast cancer patients and controls. Seven of 16 patients (43.7%) with stomach cancer, one of 8 (12.5%) with liver cancer, and one of 7 (14.3%) with breast cancer showed higher TGF-ß1 levels compared to controls. Plasma TGF-ß1 concentrations of five leukemic children remained in the normal range regardless of the remission state. In contrast, initial high TGF-ß1 levels from two children with solid tumors returned to normal range on surgical resection of tumors. From the above results, we could conclude that plasma TGF-ß1 levels of apparently healthy individuals seem to be rather constant irrespective of difference in age or sex, and the plasma TGF-ß1 has the limited value as a screening test for the diagnosis of aforementioned adult cancers because of its low sensitivity. Finally, additional studies need to be pursed for the large number of stomach cancer and pediatric solid tumor patients in order to reach a secure conclusion on the usefulness of plasma TGF-ß1 as a tumor marker in these patients.

정상 후두상피, 후두이형성증 및 후두암에서의 Transforming Growth Factor-β1 발현

진영완,이동엽,차창일,박상훈,홍남표,안회영 대한이비인후과학회 1999 대한이비인후과학회지 두경부외과학 Vol.42 No.4

정상 및 급성 신우신염 소아에서 요 Transforming Growth Factor-β1/Creatinine 비에 관한 연구

한혜원 ( Han Hye Won ),이준호 ( Lee Jun Ho ),엄은영 ( Eom Eun Yeong ),하일수 ( Ha Il Su ),정해일 ( Jeong Hae Il ),최용 ( Choe Yong ) 대한신장학회 2003 Kidney Research and Clinical Practice Vol.22 No.5

목 적 : 소아에서 만성 신부전의 원인 중 신우신염이 중요한 인자이며 transforming growth factor-β1 (TGF-β1)은 신 섬유화를 초래하는 인자임이 확인되어 있다. 본 연구는 소아의 급성 신우신염에서 요 TGF-β1/creatinine 비의 변화를 확인하고 신반흔 혹은 농뇨와의 연관성을 검증하기 위해 시행되었다. 방 법 : 정상 소아 67명과 급성 신우신염 환자 25명의 요를 채취하여 ELISA법으로 TGF-β1을 정량하였다. 요 creatinine은 alkaline picrate법으로 측정하였다. 환자의 요 TGF-β1,/creatinine 비를 대조군과 비교하고 치료후 변화를 관찰하였다. 요 TGF-β1/creatinine 비와 농뇨의 정도, 신 반흔 존재와의 연관성을 검증하였다. 결 과 : 정상 소아의 요 TGF-β1/creatinine 비는 연령이 증가함에 따라 유의하게 감소하였다 (p<0.05). 대조군에 비해 급성 신우신염 군에서 요 TGF-β1/creatinine 비는 현저히 높고 (p<0.05) 치료 후 감소하였으며 농뇨의 정도나신 반흔 발생과는 연관이 없었다. 결 론 : 소아에서 요 TGF-β1/creatinine 비는 연령별 참고치를 기준으로 평가하여야 한다. 급성 신우신염 초기의 요 TGF-β1의 증가는 가역적이고 농뇨의 정도나 신 반흔의 존재와는 무관하다. Background : Pyelonephritis is one of the major causes of chronic renal failure in children, and the transforming growth factor- R 1 (TGF-β 1) is a molecule with pivotal roles in fibrogenesis. This study was performed to investigate the alteration and clinical implications of urinary TGF- R llcreatinine ratio in children with acute pyelonephritis. Methods: Urine was collected from 67 normal children and 25 children with acute pyelonephritis. After routine urinalysis, urine TGF P 1 was quantitated by ELISA method and creatinine was measured by alkaline picrate method. Urinary TGF-β l/ creatinine ratios in children with pyelonephritis were compared with those of age-matched controls, and sequential changes of the ratios in pyelonephritic children were traced after antibiotic treatment. Correlation of urinary TGF-β 1/ creatinine ratio with the degree of pyuria and renal scar was analyzed each. Results : Neonates showed higher urinary TGF-β l/creatinine ratios than older children. The ratio increased in acute pyelonephritis and gradually returned to the control level two days after antibiotic treatment. Urinary T G F Rl/creatinine ratio in acute pyelonephritis was not correlated with the degree of pyuria and renal scar. Conclusion: The age should be considered in evaluation of urinary TGF- β l/creatinine ratio in children. The ratio increases in acute pyelonephritis, and is independent of the degree of pyuria or renal scarring.

암 환자의 혈장 Transforming Growth Factor-β1 농도

전지현(Ji-Hyun Jeon),이시은(Si-Eun Lee),이수진(Sue-Jin Lee),박찬후(Chan-Hoo Park),장정순(Joung Soon Jang),하우송(Woo Song Ha),박순태(Soon Tae Park),박병규(Byung-Kiu Park) 대한의생명과학회 1999 Biomedical Science Letters Vol.5 No.2

한국인의 대표적인 성인 고형 종양인 위암, 간암, 유방암과 소아 백혈병 및 2종의 소아 고형 종양 환자로부터 혈장 transforming growth factor-β1 (TGF-β1) 농도를 sandwich ELISA 분석법을 이용해 측정함으로써 TGF-β1을 이 질환들에 대한 새로운 종양표지자 (tumor marker)로 사용할 수 있는지 검토하였다. 또한 연령 및 성별에 따른 혈장 TGF-β1 농도의 정상치를 조사하였다. 신생아에서 70대까지 혈장 TGF-β1 농도의 차이는 없었고 남녀간의 차이도 없었다. 위암 환자의 혈장 TGF-β1 농도는 16.0±6.8 ng/㎖ (평균±표준편차)로 정상 대조군의 TGF-β1 농도 (8.3±5.0 ng/㎖) 보다 유의하게 높았으나 간암, 유방암 환자의 혈장 TGF-β1 농도는 대조군과 차이가 없었다. 그리고 위암 환자 16명, 간암 환자 8명, 유방암 환자 7명 중 각각 7명 (43.7%), 1명 (12.5%), 1명 (14.3%)에서만 혈장 TGF-β1 농도가 증가되었다. 5명의 소아 백혈병 환자에서는 관해 (remission) 여부와 상관없이 혈장 TGF-β1 농도가 모두 정상 범위에 있었으나 2명의 소아 고형암 환자에서는 종양 절제 전에는 혈장 TGF-β1 농도가 높았다가 절제 후 정상으로 떨어졌다. 결론적으로 1) 정상인의 혈장 TGF-β1 농도는 연령 및 성별에 따른 차이가 없다는 것을 알 수 있었고, 2) 성인 고형암인 위암, 간암, 유방암에서는 낮은 민감도로 인해 TGF-β1을 진단을 위한 선별 검사로 이용하기에는 부적절한 것으로 판단되었으며, 3) 정상 대조군보다 혈장 TGF-β1 농도가 높았던 위암 환자와 종양 절제 전후로 혈장 TGF-β1 농도가 민감하게 변했던 소아 고형암 환자에 대해서는 향후 표본 수를 늘려 부가적인 연구를 해야 할 것으로 사료된다. To evaluate the usefulness of transforming growth factor-β1 (TGF-β1) as a new tumor marker, we determined the plasma TGF-β1 levels using sandwich ELISA assay in cancer patients. Patients with three most common adult cancers in Korea (stomach, liver and breast cancer) and children's cancers (leukemia and two kinds of solid tumor) were enrolled for the study. Furthermore, 39 individuals were subjected to age and sex-stratified plasma TGF-β1 analysis. No statistical difference was demonstrated with respect to age or sex. The mean plasma TGF-β1 level (16.0 ng/㎖) of stomach cancer patients was significantly higher than that (8.3 ng/㎖) of controls. However, there was no difference among the mean plasma TGF-β1 levels of liver, breast cancer patients and controls. Seven of 16 patients (43.7%) with stomach cancer, one of 8 (12.5%) with liver cancer, and one of 7 (14.3%) with breast cancer showed higher TGF-β1 levels compared to controls. Plasma TGF-β1 concentrations of five leukemic children remained in the normal range regardless of the remission state. In contrast, initial high TGF-β1 levels from two children with solid tumors returned to normal range on surgical resection of tumors. From the above results, we could conclude that plasma TGF-β1 levels of apparently healthy individuals seem to be rather constant irrespective of difference in age or sex, and the plasma TGF-β1 has the limited value as a screening test for the diagnosis of aforementioned adult cancers because of its low sensitivity. Finally, additional studies need to be pursed for the large number of stomach cancer and pediatric solid tumor patients in order to reach a secure conclusion on the usefulness of plasma TGF-β1 as a tumor marker in these patients.

타목시펜이 간세포암 세포주의 성장과 Transforming Growth Factor-β 1의 발현에 미치는 영향

신정우,정영화,박무인,김정아,최민희,이윤정,류수형,박능화,이한주,이영상,서동진,유은실 대한간학회 2003 Clinical and Molecular Hepatology(대한간학회지) Vol.9 No.1

목적: 타목시펜을 진행성 간세포암 환자에게 투여한 결과 일부에서 효과가 있었다는 보고가 있으나 타목시펜이 간세포암의 성장을 억제하는 기전은 밝혀져 있지 않다. TGF-β1은 간세포암의 성장과 분화에 관여하는 중요한 성장인자로 알려져 있으며 최근 타목시펜이 TGF-β1의 분비조절에도 관여한다는 보고들이 있었다. 따라서 본 연구에서는 타목시펜이 간세포암의 성장과 TGF-β1의 발현에 미치는 영향을 알아보고 궁극적으로 타목시펜이 간세포암 환자에게 항암제로 사용될 수 있는지를 알아보고자 하였다. 대상과 방법: 인간 간세포암 세포주인 Hep 3B세포를 에스트로겐이 없는 RPMI 1640과 dextran coated charcoal로 처리한 5% fetal bovine serum을 혼합한 배지에서 3일 배양 후 2×10^4 세포/well로 분주하여 2일간 배양한 후 0.1 μM, 0.5 μM, 1 μM, 5 μM, 10 μM 농도의 타목시펜으로 처치하고 6일간 배양하였다. 매일 세포를 수집하여 trypan blue로 염색한 후 생존 세포수를 산출하였으며 상층액내 TGF-β1 농도는 ELISA법으로 측정하였다. 결과: 비교적 저 농도인 0.1 μM 타목시펜 처치군은 배양 6일째 생존 세포수가 대조군에 비해 의미 있게 증가하였다(2.59×10^6 vs 1.97×10^6, p<0.05). 생존 세포수는 타목시펜농도가 증가할수록 감소하여 10 μM 처치군은 대조군에 비해 의미있는 감소를 보였다(1.4×10^6 vs 1.97×10^6., p<0.05). 상층액내의 TGF-β1dml 분비량은 타목시펜 처치 농도와 상관없이 전 군에서 대조군에 비해 의미있게 감소하였으며 타목시펜 농도에 따른 각 군간에 차이는 없었다. 결론: 타목시펜은 실험실내에서 처치 농도에 따라 간세포암 세포주의 성장에 미치는 영향이 다양했으나, 처치 농도와 관계없이 일정한 정도로 TGF-β1의 발현을 억제하였다. 타목시펜의 이러한 효과는 생체에서 TGF-β1이 과발현된 간세포암의 성장과 진행을 억제할 것으로 생각된다. 또한 타목시펜은 TGF-β1의 발현을 조절하는 기전 이외의 다른 기전을 통해서는 간세포암의 성장을 억제하는 것으로 사료된다. Background/Aims: Tamoxifen has been tried in patients with hepatocellular carcinoma (HCC), however, its inhibitory mechanism remains unknown. In this study, we evaluated the effects of tamoxifen on HCC cell growth and the expression of transforming growth factor-β1 (TGF-β1) which had been known as an important cytokine in growth of HCC. Methods: Hep 3B cells were cultivated in estrogen free media with 0.1 μM, 0.5 μM, 1 μM, 5 μM, and 10μM of tamoxifen for 6 days. Viable cells were counted daily and the TGF-β1 concentrations in supernatant were measured by ELISA method. Results: The number of viable HCC cells increased rather significantly after the treatment of tamoxifen of lower concentration (0.1 μM) compared with that of the control (2.57×10^7 us. 1.97×10^7; p<0.05). As the concentration of treated tamoxifen was higher, the number of viable HCC cells became gradually less, resulting in the significant decrease of it at the highest concentration (10 μM) compared with that of the control (1.40×10^7 us. 1.97×10^7; p<0.05). TGF-β1 concentration in supernatant of tamoxifen-treated samples was significantly decreased compared with those of controls, regardless of the amount of treated tamoxifen. Conclusions: These results suggest that tamoxifen may suppress TGF-β1 expression to an extent, although it has different effects on the proliferation of HCC cells, at the various concentrations of this agent in vitro. Such effects of tamoxifen on TGF-β expression may inhibit the growth and progression of HCCs over-expressing TGF-β1 in vivo.