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[1]赵 勇,任建琳,严玉婷,等.健脾通络方通过调控TGF-β1/SMAD4信号通路抑制结直肠癌细胞上皮-间充质转化的机制研究[J].国际消化病杂志,2024,06:387-392.
 ZHAO Yong,REN Jianlin,YAN Yuting,et al.Effects and mechanism of JPTLR in inhibiting epithelial-mesenchymal transition in colorectal cancer cells by regulating the TGF-β1/SMAD4 signaling pathway[J].International Journal of Digestive Disease,2024,06:387-392.
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健脾通络方通过调控TGF-β1/SMAD4信号通路抑制结直肠癌细胞上皮-间充质转化的机制研究(PDF)

《国际消化病杂志》[ISSN:1673-534X/CN:31-1953/R]

期数:
2024年06期
页码:
387-392
栏目:
论著
出版日期:
2024-12-20

文章信息/Info

Title:
Effects and mechanism of JPTLR in inhibiting epithelial-mesenchymal transition in colorectal cancer cells by regulating the TGF-β1/SMAD4 signaling pathway
作者:
赵 勇任建琳严玉婷周 霖储金砚袁晨越
200071 上海中医药大学附属市中医医院肿瘤科
Author(s):
ZHAO Yong REN Jianlin YAN Yuting ZHOU Lin CHU Jinyan YUAN Chenyue
Department of Oncology, Shanghai Municipal Hospital of Traditional Chinese Medicine Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai 200071, China
关键词:
结直肠癌健脾通络方上皮-间充质转化侵袭迁移
Keywords:
Colorectal cancer Jianpi Tongluo Recipe Epithelial-mesenchymal transition InvasionMigration
分类号:
-
DOI:
10.3969/j.issn.1673-534X.2024.06.008
文献标识码:
-
摘要:
目的探究健脾通络方(JPTLR)对结直肠癌(CRC)细胞增殖、侵袭、迁移和上皮-间充质转化(EMT)的影响及作用机制。方法构建转化生长因子-β(TGF-β)高表达的HCT116细胞模型。将HCT116细胞分为对照(NC)组、NC+TGF-β1组、JPTLR组、JPTLR+TGF-β1组、LY2109761组和LY2109761+TGF-β1组。采用细胞划痕愈合实验和Transwell侵袭实验分别检测各组细胞的迁移、侵袭能力。采用蛋白质印迹法检测各组细胞中TGF-β1、SMAD4及EMT相关蛋白表达水平。结果与NC组相比,JPTLR组的细胞划痕愈合率降低,细胞侵袭数量减少,SMAD4和波形蛋白(Vimentin)表达水平均显著降低,E-钙黏蛋白(E-cadherin)和紧密连接蛋白-1(Claudin-1)表达水平均显著升高,差异均有统计学意义(P均<0.05)。与NC+TGF-β1组相比,JPTLR+TGF-β1组的SMAD4和Vimentin表达水平均显著降低,E-cadherin和Claudin-1表达水平均显著升高,差异均有统计学意义(P均<0.05)。结论JPTLR通过下调HCT116细胞中SMAD4的表达,使E-cadherin、Claudin-1表达水平升高,Vimentin表达水平降低,从而抑制CRC细胞的增殖、侵袭、迁移及EMT。
Abstract:
Objective? This paper attempts to investigate the effects and mechanisms of Jianpi Tongluo Recipe (JPTLR) on the proliferation, invasion, migration, and epithelial-mesenchymal transition (EMT) of colorectal cancer (CRC) cells. Methods? A high-expression transforming growth factor-β (TGF-β) HCT116 cell model was established. The HCT116 cells were divided into six groups: control (NC) group, NC+TGF-β1 group, JPTLR group, JPTLR+TGF-β1 group, LY2109761 group, and LY2109761+TGF-β1 group. The scratch healing assay and Transwell invasion assay were used to evaluate cell migration and invasion. The expression levels of TGF-β1, SMAD4, and EMT-related proteins were detected by Western blotting. Results? Compared to the NC group, the JPTLR group shows a significantly lower cell scratch healing rate, reduced number of invasive cells, decreased expression of SMAD4 and Vimentin, and increased expression of E-cadherin and Claudin-1, with statistically significant differences (P<0.05). Compared to the NC+TGF-β1 group, the expression of SMAD4 and Vimentin in the JPTLR+TGF-β1 group are decreased; the expression of E-cadherin and Claudin-1 are increased, with statistically significant differences (P<0.05). Conclusion? JPTLR inhibits the proliferation, invasion, migration, and EMT of CRC cells by downregulating SMAD4 expression, increasing the expression of E-cadherin and Claudin-1, and decreasing the expression of Vimentin in HCT116 cells.

参考文献/References

1Underwood PW, Ruff SM, Pawlik TM. Update on targeted therapy and immunotherapy for metastatic colorectal cancer[J]. Cells, 2024, 13(3): 245.
2Franco DL, Mainez J, Vega S, et al. Snail1 suppresses TGF-beta-induced apoptosis and is sufficient to trigger EMT in hepatocytes[J]. J Cell Sci, 2010, 123(Pt 20): 3467-3477.
3Thiery JP, Acloque H, Huang RY, et al. Epithelial-mesenchymal transitions in development and disease[J]. Cell, 2009, 139(5): 871-890.
4Tsushima H, Kawata S, Tamura S, et al. High levels of transforming growth factor beta 1 in patients with colorectal cancer: association with disease progression[J]. Gastroenterology, 1996, 110(2): 375-382.
5 张彦博, 刘宣, 季青, 等. 健脾解毒方联合化疗治疗转移性结直肠癌临床研究[J]. 中华中医药杂志, 2015, 30(6): 2090-2093.6 陈文婷, 任建琳, 石齐, 等. 中西医结合治疗大肠癌的回顾性研究及对生存预后影响因素的分析[J]. 广州中医药大学学报, 2015, 32(2): 234-238, 242.
7Scimeca M, Giannini E, Antonacci C, et al. Microcalcifications in breast cancer: an active phenomenon mediated by epithelial cells with mesenchymal characteristics[J]. BMC Cancer, 2014, 14: 286.
8Bullock MD, Sayan AE, Packham GK, et al. MicroRNAs: critical regulators of epithelial to mesenchymal (EMT) and mesenchymal to epithelial transition (MET) in cancer progression[J]. Biol Cell, 2012, 104(1): 3-12.
9Nakajima S, Doi R, Toyoda E, et al. N-cadherin expression and epithelial-mesenchymal transition in pancreatic carcinoma[J]. Clin Cancer Res, 2004, 10(12 Pt 1): 4125-4133.
10 Haslehurst AM, Koti M, Dharsee M, et al. EMT transcription factors snail and slug directly contribute to cisplatin resistance in ovarian cancer[J]. BMC Cancer, 2012, 12: 91.
11 Huber MA, Kraut N, Beug H. Molecular requirements for epithelial-mesenchymal transition during tumor progression[J]. Curr Opin Cell Biol, 2005, 17(5): 548-558.
12 Moustakas A, Heldin CH. Signaling networks guiding epithelial-mesenchymal transitions during embryogenesis and cancer progression[J]. Cancer Sci, 2007, 98(10): 1512-1520.
13 Wakefield LM, Roberts AB. TGF-beta signaling: positive and negative effects on tumorigenesis[J]. Curr Opin Genet Dev, 2002, 12(1): 22-29.
14 Xie L, Law BK, Chytil AM, et al. Activation of the Erk pathway is required for TGF-beta1-induced EMT in vitro[J]. Neoplasia, 2004, 6(5): 603-610.
15 Stadler SC, Vincent CT, Fedorov VD, et al. Dysregulation of PAD4-mediated citrullination of nuclear GSK3β activates TGF-β signaling and induces epithelial-to-mesenchymal transition in breast cancer cells[J]. Proc Natl Acad Sci U S A, 2013, 110(29): 11851-11856.
16 Park KS, Dubon MJ, Gumbiner BM. N-cadherin mediates the migration of MCF-10A cells undergoing bone morphogenetic protein 4-mediated epithelial mesenchymal transition[J]. Tumour Biol, 2015, 36(5): 3549-3556.

备注/Memo

备注/Memo:
基金项目:上海市科技创新行动计划生物医药科技支撑专项(22S21901000);国家自然科学基金面上项目(82174452、81873279);上海医学创新发展基金会-中医药科技发展项目(WLJH2021ZY-MZY026);上海申康医院发展中心临床三年行动计划疑难疾病精准诊治攻关项目(SHDC2020CR2047B)
通信作者:任建琳,Email: renjianlin666@126.com
更新日期/Last Update: 2024-12-20