Issue
Luteolin affects keloid fibroblast proliferation and apoptosis by regulating FRAT1 gene expression
Corresponding Author(s) : Wen Liu
Cellular and Molecular Biology,
Vol. 66 No. 3: Issue 3
Abstract
The current experiment was performed to investigate whether luteolin affects the proliferation and apoptosis of keloid fibroblasts by regulating the expression of FRAT1 gene. Keloid fibroblasts were treated with luteolin at different concentrations. MTT method, western blot, flow cytometry, and real-time quantitative PCR (qPCR) were used to detect cell proliferation, cyclin D1 (CyclinD1), p21, B-cell lymphoma / leukemia-2 (Bcl-2), Bcl-2 related X protein (Bax), FRAT1 protein expression, apoptosis and ARHI mRNA expression. Keloid fibroblasts were transfected with si-FRAT1, or pcDNA-FRAT1 and treated with luteolin to observe their roles in cell proliferation and apoptosis. Compared with the control group, luteolin significantly reduced the keloid fibroblast activity, CyclinD1, Bcl-2, and FRAT1 protein levels, and obviously improved the cell apoptosis rate, p21 and Bax protein expression (P<0.05). The expression of FRAT1 mRNA and protein in keloid fibroblasts was greatly increased (P<0.05). Inhibition of FRAT1 expression evidently decreased cell viability at 24 h, 48 h, and 72 h, CyclinD1, and Bcl-2 protein expression of keloid fibroblasts, while-dramatically enhanced cell apoptosis, p21, and Bax protein levels (P<0.05). FRAT1 overexpression reversed the inhibitory effect of luteolin on keloid fibroblast activity, FRAT1, CyclinD1, and Bcl-2 protein expression, and promotion of apoptosis, p21 and Bax protein expression. Luteolin can inhibit the proliferation and induce apoptosis of keloid fibroblasts by regulating the expression of FRAT1 gene.
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- . Chen ZY, Yu XF, Huang JQ, Li DL. The mechanisms of β-catenin on keloid fibroblast cells proliferation and apoptosis. Eur Rev Med Pharmacol 2018; 22:888-95.
- Austin E, Koo E, Jagdeo J. The cellular response of keloids and hypertrophic scars to botulinum toxin A: a comprehensive literature review. Dermatol Surg 2018; 44(2): 149-157.
- Hietanen KE, Järvinen TA, Huhtala H, Tolonen TT, Kuokkanen HO, Kaartinen IS. Treatment of keloid scars with intralesional triamcinolone and 5-fluorouracil injections–a randomized controlled trial. J Plast Reconstr Aesthet Surg 2019; 72(1): 4-11.
- Hu Y, Chen X, Li Z, Zheng S, Cheng Y. Thermosensitive in situ gel containing luteolin micelles is a promising efficient agent for colorectal cancer peritoneal metastasis treatment. J Biomed Nanotechnol 2020; 16(1):54-64.
- Ren Kaiming, Zhou Zhaoli, Shi Wenjun. Effects of luteolin on the proliferation, apoptosis, invasion and migration of human non-small cell lung cancer A549 cells. Progr Anatom Sci 2019; 25 (4): 361-363.
- Zhao Changqi, Zhao Yaohong, Yu Hailong. Effects of luteolin on proliferation and apoptosis of mouse T lymphocytes in vitro.China Journal of Experimental Traditional Medical Formulae, 2018;24(22):133-137.
- Meng Xin, Zhong Weiqing, Zhang Xinrong. Effect of luteolin on proliferation and angiogenic activity of hepatocellular carcinoma HepG2 cells in vitro. J Hainan M Un 2017,23(23):3195-3198.
- Zheng X, Qu N, Zheng K. Effects of Frat1 on proliferation and apoptosis of non-small cell lung cancer A549 cells via Wnt/β-catenin signaling pathway. J Clinic Pulmonary Med 2019,24(10):1855-1859.
- Guo G, Zhang X, Kuai D. Expression and significance of FRAT1 gene in human brain gliocytoma . Chin J Clinic 2013; 7(20): 9107-9110.
- Wang S, Yu Q, Gu W. Effect of FRAT1 gene silencing on proliferation and apoptosis of colon cancer HT-29 cells and possible relevant mechanism . Chin J Lab Diag 2014; 18(2): 195-199.
- Yang L, Han Yan, Li Huiyuan. Expression and distribution of SMAD3 in keloid fibroblasts. Chin J Aesthetic Med 2003; 12(1):14-16+120.
- Jian X, Qu L, Wang Y, Zou Q, Zhao Q, Chen S, Gao X, Chen H, He C. Trichostatin A-induced miR 30a 5p regulates apoptosis and proliferation of keloid fibroblasts via targeting BCL2. Mol Med Rep 2019; 19(6):5251-62.
- Hou Z, Fan F, Liu P. BTXA regulates the epithelial-mesenchymal transition and autophagy of keloid fibroblasts via modulating miR-1587/miR-2392 targeted ZEB2. Biosci Rep 2019; 39(10): BSR20190679.
- Pang Q, Wang Y, Xu M, Xu J, Xu S, Shen Y, Xu J, Lei R. MicroRNA-152-5p inhibits proliferation and migration and promotes apoptosis by regulating expression of Smad3 in human keloid fibroblasts. BMB Rep 2019; 52(3):202.
- Iida K, Naiki T, Naiki"Ito A, Suzuki S, Kato H, Nozaki S, Nagai T, Etani T, Nagayasu Y, Ando R, Kawai N. Luteolin suppresses bladder cancer growth via regulation of mechanistic target of rapamycin pathway. Cancer Sci 2020; 111(4):1165.
- Moeng S, Son SW, Seo HA, Lee JS, Kim CK, Kuh HJ, Park JK. Luteolin-regulated MicroRNA-301-3p Targets Caspase-8 and Modulates TRAIL Sensitivity in PANC-1 Cells. Anticancer Res 2020; 40(2):723-31.
- Ambasta RK, Gupta R, Kumar D, Bhattacharya S, Sarkar A, Kumar P. Can luteolin be a therapeutic molecule for both colon cancer and diabetes?. Brief Funct Genomics 2019; 18(4):230-9.
- Fan JJ, Hsu WH, Lee KH, Chen KC, Lin CW, Lee YL, Ko TP, Lee LT, Lee MT, Chang MS, Cheng CH. Dietary Flavonoids Luteolin and Quercetin Inhibit Migration and Invasion of Squamous Carcinoma through Reduction of Src/Stat3/S100A7 Signaling. Antioxidants 2019; 8(11):557.
- Lee Y, Kwon Y H. Regulation of apoptosis and autophagy by luteolin in human hepatocellular cancer Hep3B cells. Biochem Biophys Res Commun, 2019, 517(4): 617-622.
- Yao X, Jiang W, Yu D, et al. Luteolin inhibits proliferation and induces apoptosis of human melanoma cells in vivo and in vitro by suppressing MMP-2 and MMP-9 through the PI3K/AKT pathway. Food Funct, 2019; 10(2): 703-712.
- . Huang L, Jin K, Lan H. Luteolin inhibits cell cycle progression and induces apoptosis of breast cancer cells through downregulation of human telomerase reverse transcriptase. Oncol Lett 2019, 17(4): 3842-3850.
- Yu Q, Shang LU, Yu H, Yang Z, Xu D. Silencing of FRAT1 by siRNA inhibits the proliferation of SGC7901 human gastric adenocarcinoma cells. Biomed Rep 2016; 4(2):223-6.
- Zhu K, Guo J, Wang H, Yu W. FRAT1 expression regulates proliferation in colon cancer cells. Oncol Lett 2016; 12(6):4761-6.
- Li X, Zheng H. LncRNA SNHG1 influences cell proliferation, migration, invasion, and apoptosis of non-small cell lung cancer cells via the miR-361-3p/FRAT1 axis. Thorac Cancer, 2020; 11(2):295-304.
- Zhang W, Xiong H, Zou Y, Xu S, Quan L, Yuan X, Xu N, Wang Y. Frequently rearranged in advanced T cell lymphomas 1 demonstrates oncogenic properties in prostate cancer. Mol Med Rep 2016; 14(4):3551-8.
- Bordbar M, Darvishzadeh R, Pazhouhandeh M, Kahrizi D. An overview of genome editing methods based on endonucleases. Modern Genetics J 2020; 15(2): 75-92.
References
. Chen ZY, Yu XF, Huang JQ, Li DL. The mechanisms of β-catenin on keloid fibroblast cells proliferation and apoptosis. Eur Rev Med Pharmacol 2018; 22:888-95.
Austin E, Koo E, Jagdeo J. The cellular response of keloids and hypertrophic scars to botulinum toxin A: a comprehensive literature review. Dermatol Surg 2018; 44(2): 149-157.
Hietanen KE, Järvinen TA, Huhtala H, Tolonen TT, Kuokkanen HO, Kaartinen IS. Treatment of keloid scars with intralesional triamcinolone and 5-fluorouracil injections–a randomized controlled trial. J Plast Reconstr Aesthet Surg 2019; 72(1): 4-11.
Hu Y, Chen X, Li Z, Zheng S, Cheng Y. Thermosensitive in situ gel containing luteolin micelles is a promising efficient agent for colorectal cancer peritoneal metastasis treatment. J Biomed Nanotechnol 2020; 16(1):54-64.
Ren Kaiming, Zhou Zhaoli, Shi Wenjun. Effects of luteolin on the proliferation, apoptosis, invasion and migration of human non-small cell lung cancer A549 cells. Progr Anatom Sci 2019; 25 (4): 361-363.
Zhao Changqi, Zhao Yaohong, Yu Hailong. Effects of luteolin on proliferation and apoptosis of mouse T lymphocytes in vitro.China Journal of Experimental Traditional Medical Formulae, 2018;24(22):133-137.
Meng Xin, Zhong Weiqing, Zhang Xinrong. Effect of luteolin on proliferation and angiogenic activity of hepatocellular carcinoma HepG2 cells in vitro. J Hainan M Un 2017,23(23):3195-3198.
Zheng X, Qu N, Zheng K. Effects of Frat1 on proliferation and apoptosis of non-small cell lung cancer A549 cells via Wnt/β-catenin signaling pathway. J Clinic Pulmonary Med 2019,24(10):1855-1859.
Guo G, Zhang X, Kuai D. Expression and significance of FRAT1 gene in human brain gliocytoma . Chin J Clinic 2013; 7(20): 9107-9110.
Wang S, Yu Q, Gu W. Effect of FRAT1 gene silencing on proliferation and apoptosis of colon cancer HT-29 cells and possible relevant mechanism . Chin J Lab Diag 2014; 18(2): 195-199.
Yang L, Han Yan, Li Huiyuan. Expression and distribution of SMAD3 in keloid fibroblasts. Chin J Aesthetic Med 2003; 12(1):14-16+120.
Jian X, Qu L, Wang Y, Zou Q, Zhao Q, Chen S, Gao X, Chen H, He C. Trichostatin A-induced miR 30a 5p regulates apoptosis and proliferation of keloid fibroblasts via targeting BCL2. Mol Med Rep 2019; 19(6):5251-62.
Hou Z, Fan F, Liu P. BTXA regulates the epithelial-mesenchymal transition and autophagy of keloid fibroblasts via modulating miR-1587/miR-2392 targeted ZEB2. Biosci Rep 2019; 39(10): BSR20190679.
Pang Q, Wang Y, Xu M, Xu J, Xu S, Shen Y, Xu J, Lei R. MicroRNA-152-5p inhibits proliferation and migration and promotes apoptosis by regulating expression of Smad3 in human keloid fibroblasts. BMB Rep 2019; 52(3):202.
Iida K, Naiki T, Naiki"Ito A, Suzuki S, Kato H, Nozaki S, Nagai T, Etani T, Nagayasu Y, Ando R, Kawai N. Luteolin suppresses bladder cancer growth via regulation of mechanistic target of rapamycin pathway. Cancer Sci 2020; 111(4):1165.
Moeng S, Son SW, Seo HA, Lee JS, Kim CK, Kuh HJ, Park JK. Luteolin-regulated MicroRNA-301-3p Targets Caspase-8 and Modulates TRAIL Sensitivity in PANC-1 Cells. Anticancer Res 2020; 40(2):723-31.
Ambasta RK, Gupta R, Kumar D, Bhattacharya S, Sarkar A, Kumar P. Can luteolin be a therapeutic molecule for both colon cancer and diabetes?. Brief Funct Genomics 2019; 18(4):230-9.
Fan JJ, Hsu WH, Lee KH, Chen KC, Lin CW, Lee YL, Ko TP, Lee LT, Lee MT, Chang MS, Cheng CH. Dietary Flavonoids Luteolin and Quercetin Inhibit Migration and Invasion of Squamous Carcinoma through Reduction of Src/Stat3/S100A7 Signaling. Antioxidants 2019; 8(11):557.
Lee Y, Kwon Y H. Regulation of apoptosis and autophagy by luteolin in human hepatocellular cancer Hep3B cells. Biochem Biophys Res Commun, 2019, 517(4): 617-622.
Yao X, Jiang W, Yu D, et al. Luteolin inhibits proliferation and induces apoptosis of human melanoma cells in vivo and in vitro by suppressing MMP-2 and MMP-9 through the PI3K/AKT pathway. Food Funct, 2019; 10(2): 703-712.
. Huang L, Jin K, Lan H. Luteolin inhibits cell cycle progression and induces apoptosis of breast cancer cells through downregulation of human telomerase reverse transcriptase. Oncol Lett 2019, 17(4): 3842-3850.
Yu Q, Shang LU, Yu H, Yang Z, Xu D. Silencing of FRAT1 by siRNA inhibits the proliferation of SGC7901 human gastric adenocarcinoma cells. Biomed Rep 2016; 4(2):223-6.
Zhu K, Guo J, Wang H, Yu W. FRAT1 expression regulates proliferation in colon cancer cells. Oncol Lett 2016; 12(6):4761-6.
Li X, Zheng H. LncRNA SNHG1 influences cell proliferation, migration, invasion, and apoptosis of non-small cell lung cancer cells via the miR-361-3p/FRAT1 axis. Thorac Cancer, 2020; 11(2):295-304.
Zhang W, Xiong H, Zou Y, Xu S, Quan L, Yuan X, Xu N, Wang Y. Frequently rearranged in advanced T cell lymphomas 1 demonstrates oncogenic properties in prostate cancer. Mol Med Rep 2016; 14(4):3551-8.
Bordbar M, Darvishzadeh R, Pazhouhandeh M, Kahrizi D. An overview of genome editing methods based on endonucleases. Modern Genetics J 2020; 15(2): 75-92.