Copyright
©The Author(s) 2021.
World J Gastrointest Oncol. Nov 15, 2021; 13(11): 1648-1667
Published online Nov 15, 2021. doi: 10.4251/wjgo.v13.i11.1648
Published online Nov 15, 2021. doi: 10.4251/wjgo.v13.i11.1648
Table 1 Studies of the transforming growth factor-β signaling pathway in drug resistance in gastrointestinal cancer
Cancer type | In vivo/In vitro | Upstream regulator | Alteration of TGF-β signaling | Effect | Downstream antitumor drug | Ref. |
CRC | SK-CO-1 cells | MED12 knockdown | The activation of TGF-β signaling or TGF-β treatment | Resistance | DDP, OXA, and 5-FU | Brunen et al[66], 2013 |
CRC | HCT116/HCT116p53KO chemoresistant cell lines | - | TGF-β1 treatment/TβRI inhibition | Resistance/sensitivity | 5-FU | Romano et al[82], 2016 |
CRC | HCT116 cells | - | Smad4 knockdown | Sensitivity | Dox | Li et al[103], 2015 |
CRC | in vivo, CRC animal model, stable OXA-resistant cell line HCT116/OXA | Curcumin | Inhibition of p-Smad2 and p-Smad3 | Sensitivity | OXA | Yin et al[90], 2019 |
CRC | The resistant cell model HCT-8/5-FU cell line | Hedyotis diffusa Willd | Inhibition of TGF-β signaling | Antimetastasis in 5-FU-resistant cells | 5-FU | Lai et al[116], 2017 |
CRC | HCT116 and DLD1 CRC cell lines | - | siRNA-mediated knockdown of SMAD2/3, TGF-β inhibitor SB431542 | Sensitivity | OXA | Kim et al[89], 2019 |
CRC | RKO cells | - | Silencing of TβRII expression, TβRI inhibitor LY2157299 | Sensitivity | BETi | Shi et al[112], 2016 |
CRC | HCT116 cells | - | TGF-β inhibitor LY2157299 | Sensitivity | 5-FU | Quan et al[81], 2019 |
CRC | CT26 cells | Chemokine C-C motif ligand-1 secreted by Snail-expression fibroblasts | Phosphorylated Smad2 | Resistance | 5-FU or paclitaxel | Li et al[143], 2018 |
CRC | 5-FU resistant cell line(HCT-8/5-FU) | Pien Tze Huang (PZH) | Suppression of TGF-β and Smad4 | Overcome MDR and inhibit EMT | - | Shen et al[117], 2014 |
CRC | Patients | - | P-Smad3 overexpression | Resistance | 5-FU and leucovorin, capecitabine | Huang et al[78], 2015 |
CRC | HCT116 Smad4+/+ and Smad4-/- cell lines | - | Smad4 defect | Resistance | 5-FU | Papageorgis et al[76], 2011 |
CRC | in vivo, colorectal tumor biopsies | - | Normal SMAD4 diploidy | Sensitivity | 5-FU and mitomycin | Boulay et al[73], 2002 |
CRC | Dukes CRC patients | - | Low SMAD4 mRNA and protein levels | Resistance | 5-FU-based adjuvant chemotherapy | Alhopuro et al[75], 2005 |
CRC | Colorectal tumor biopsies | - | The amplification of STRAP, an inhibitor of TGF-β signaling | Resistance | 5-FU /mitomycin C adjuvant chemotherapy | Buess et al[74], 2004 |
CRC | Colo205 and RKO cells | - | TGF-β1 treatment | Resistance | 5-FU, etoposide | Moon et al[80], 2019 |
CRC | Mouse models | - | Blockade of TGF-β signaling | Sensitivity | Anti-PD-1-PD-L1 checkpoint therapy | Tauriello et al[115], 2018 |
CRC | Mice models of MC38-derived tumors | - | 1D11 antibody anti-TGF-β mAb | Sensitivity | Anti-PD1 plus anti-CD137 mAb | Rodríguez-Ruiz et al[114], 2019 |
CRC | SNU-C5/5-FU -resistant cells. | (1S,2S,3E,7E,11E)-3,7,11,15-cembratetraen-17,2-olide (LS-1) from Lobophytum sp | The increase of Smad-3 phosphorylation and the nuclear localization of p-Smad3 and Smad4 | Sensitivity | 5-FU | Kim et al[118], 2015 |
CRC | The early stages of colorectal carcinogenesis in rats | 5-FU/thymoquinone (TQ) combination therapy | Upregulation of the TGF-β1, TβRII, Smad4 | Sensitivity | 5-FU | Kensara et al[122], 2016 |
CRC | Azoxymethane (AOM) rat model | Vitamin D3/5-FU co-therapy | Upregulation of the TGF-β1, TβRII, smad4 | Sensitivity | 5-FU | Refaat et al[77], 2015 |
CRC | RKO cells | Oxymatrine | Inhibition of the Smad2 phosphorylation and the formation of Smad2/3/4 | Sensitivity | - | Wang et al[119], 2017 |
EC | Paclitaxel-resistant EC109 cells | - | BMP-4 and p-Smad1/5 overexpression | Resistance | Paclitaxel | Zhou et al[100], 2017 |
ESCC | KYSE-150 and KYSE-180 cells, xenograft tumors in nude mice | - | TβRI inhibitor LY2157299 | Sensitivity | DDP and taxol | Zhang et al[142], 2017 |
ESCC | Xenotransplanted tumor mice model | - | Dual PD-1/PD-L1 and TGF-β blockades | Sensitivity | PD-1/PD-L1 blockade | Chen et al[139], 2018 |
EC and GC | EC cells T.T, GC cells MKN28 and MKN45 | - | Pretreatment with TGF-β | Sensitivity | Adriamycin | Izutani et al[104], 2002 |
EAC | EAC cells, EAC patient-derived xenograft tumors | - | TβR inhibitor and trastuzumab, pertuzumab | Sensitivity | Trastuzumab and Pertuzumab | Ebbing et al[106], 2017 |
EC | KYSE150 andKYSE450 cells | Garcinol | Inhibition of the p300/CBP and p-Smad2/3 expression | Sensitivity | - | Wang et al[120], 2020 |
ESCC | Patients | - | High serum levels of VEGF-A and TGF-β1 | Resistance | Taxane-based/5-FU -based chemotherapy | Cheng et al[79], 2014 |
ESCC | TE1 | - | Anti-TGF-β2 neutralizing mAb and SB-431542 | Sensitivity | Trastuzumab | Mimura et al[110], 2005 |
ESCC | TE1/TE5 | - | Anti-TGF-β2 neutralizing mAb/exogenous addition of TGF-β2 | Sensitivity/resistance | Cetuximab | Kawaguchi et al[109], 2007 |
ESCC | ECA109 and TE1 cells | Overexpression of LEF1 | Upregulation of p-Smad2, p-Smad3, and TGF-β | Resistance | DDP | Zhao et al[130], 2019 |
GC | AGS cells | Glycoprotein from the Capsosiphon fulvescens | Inhibition of TGF-β1-activated FAK/PI3K/AKT pathways | Sensitivity | - | Kim et al[121], 2013 |
GC | SGC7901 and BGC823 cells | HMMR | Upregulation of p-Smad2 level and the nuclearaccumulation of Smad2 | Resistance | 5-FU | Zhang et al[84], 2019 |
GC | A peritoneal-metastatic cell line, 60As6 | - | TGF-β treatment | Sensitivity | Docetaxel | Fujita et al[99], 2015 |
GC | MKN-45 cells | Eribulin | Inhibition of the TGF-β/Smad pathway | Sensitivity | - | Kurata et al[126], 2018 |
GC | Peritoneal mesothelial cells (HPMCs) | Paclitaxel | Inhibition of phosphorylation of Smad2 | Reduce stromal fibrosis | - | Tsukada et al[98], 2013 |
GC | NCI-N87 cells | - | TGF-β treatment | Resistance | Trastuzumab | Zhou et al[107], 2018 |
AGS and MKN45 cells | MSCs | Activated TGF-β signaling | Resistance | 5-FU and OXA | He et al[146], 2019 | |
CRC | Patients | - | TGF-β2 expression | Sensitivity | Fluoropyrimidine | Kim et al[68], 2009 |
- Citation: Lv X, Xu G. Regulatory role of the transforming growth factor-β signaling pathway in the drug resistance of gastrointestinal cancers. World J Gastrointest Oncol 2021; 13(11): 1648-1667
- URL: https://www.wjgnet.com/1948-5204/full/v13/i11/1648.htm
- DOI: https://dx.doi.org/10.4251/wjgo.v13.i11.1648