Abstract：Insensitivity of tumor cells to chemotherapeutic agents and arising drug resistance are the main cause of high mortality in gastric cancer. Epithelial mesenchymal transformation (EMT) plays an important role in the progression of gastric cancer. There is mounting evidence demonstrating that EMT participates in gastric cancer chemotherapeutic drug resistance through related transcription factors, cytokines, important signaling pathways, and regulation of stemness. This article summarizes the relationship between EMT and chemoresistance in gastric cancer to help people find new strategies in anti-drug-resistant treatment of gastric cancer.
陈梦娇1 徐岷2. 胃癌上皮间质转化与化疗耐药性关系的研究进展[J]. 中国医药导报, 2019, 16(13): 46-49.
CHEN Mengjiao1 XU Min2. Research progress on the relationship between epithelial-mesenchymal transition and chemoresistance in gastric cancer. 中国医药导报, 2019, 16(13): 46-49.
[1] Bray F，Ferlay J，Soerjomataram I，et al. Global cancer statistics 2018：GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries [J]. CA Cancer J Clin，2018，68（6）：394-424.
[2] Peng Z，Wang CX，Fang EH，et al. Role of epithelial-mesenchymal transition in gastric cancer initiation and progression [J]. World J Gastroenterol，2014，20（18）：5403-5410.
[3] Nieto MA，Huang RY，Jackson RA，et al. Emt：2016 [J]. Cell，2016，166（1）：21-45.
[4] Fodale V，Pierobon M，Liotta L，et al. Mechanism of cell adaptation：when and how do cancer cells develop chemoresistance？[J]. Cancer J，2011，17（2）：89-95.
[5] Shi WJ，Gao JB. Molecular mechanisms of chemoresistance in gastric cancer [J]. World J Gastrointest Oncol，2016，8（9）：673-681.
[6] Voon DC，Huang RY，Jackson RA，et al. The EMT spectrum and therapeutic opportunities [J]. Mol Oncol，2017， 11（7）：878-891.
[7] Huang D，Duan H，Huang H，et al. Cisplatin resistance in gastric cancer cells is associated with HER2 upregulation-induced epithelial-mesenchymal transition [J]. Sci Rep，2016，6：20502.
[8] Jiang T，Dong P，Li L，et al. MicroRNA-200c regulates cisplatin resistance by targeting ZEB2 in human gastric cancer cells [J]. Oncol Rep，2017，38（1）：151-158.
[9] Geng DM，Kan XM，Zhang WW. Effect of ZEB2 silencing on cisplatin resistance in gastric cancer [J]. Eur Rev Med Pharmacol Sci，2017，21（8）：1746-1752.
[10] Kang X，Li M，Zhu H，et al. DUSP4 promotes doxorubicin resistance in gastric cancer through epithelial-mesenchymal transition [J]. Oncotarget，2017，8（55）：94028-94039.
[11] Zhou X，Men X，Zhao R，et al. miR-200c inhibits TGF-beta-induced-EMT to restore trastuzumab sensitivity by targeting ZEB1 and ZEB2 in gastric cancer [J]. Cancer Gene Ther，2018，25（3/4）：68-76.
[12] Oh SC，Sohn BH，Cheong JH，et al. Clinical and genomic landscape of gastric cancer with a mesenchymal phenotype [J]. Nat Commun，2018，9（1）：1777.
[13] Banerjee AS，Pal AD，Banerjee S. Epstein-Barr virus-encoded small non-coding RNAs induce cancer cell chemoresistance and migration [J]. Virology，2013，443（2）：294-305.
[14] Kuai WX，Wang Q，Yang XZ，et al. Interleukin-8 associates with adhesion，migration，invasion and chemosensitivity of human gastric cancer cells [J]. World J Gastroenterol，2012，18（9）：979-985.
[15] Kim HP，Han SW，Song SH，et al. Testican-1-mediated epithelial-mesenchymal transition signaling confers acquired resistance to lapatinib in HER2-positive gastric cancer [J]. Oncogene，2014，33（25）：3334-3341.
[16] Zhang Z，Wang J，Ji D，et al. Functional genetic approach identifies MET，HER3，IGF1R，INSR pathways as determinants of lapatinib unresponsiveness in HER2-positive gastric cancer [J]. Clin Cancer Res，2014，20（17）：4559-4573.
[17] Lee YY，Kim HP，Kang MJ，et al. Phosphoproteomic analysis identifies activated MET-axis PI3K/AKT and MAPK/ERK in lapatinib-resistant cancer cell line [J]. Exp Mol Med，2013，45：e64.
[18] Yoon C，Cho SJ，Aksoy BA，et al. Chemotherapy Resistance in Diffuse-Type Gastric Adenocarcinoma Is Mediated by RhoA Activation in Cancer Stem-Like Cells [J]. Clin Cancer Res，2016，22（4）：971-983.
[19] Shibue T，Weinberg RA. EMT，CSCs，and drug resistance：the mechanistic link and clinical implications [J]. Nat Rev Clin Oncol，2017，14（10）：611-629.
[20] Bagheri V，Memar B，Behzadi R，et al. Isolation and identification of chemotherapy-enriched sphere-forming cells from a patient with gastric cancer [J]. J Cell Physiol，2018，233（10）：7036-7046.
[21] Wang B，Chen Q，Cao Y，et al. LGR5 Is a Gastric Cancer Stem Cell Marker Associated with Stemness and the EMT Signature Genes NANOG，NANOGP8，PRRX1，TWIST1，and BMI1 [J]. PLoS One，2016，11（12）：e0168904.
[22] Ma X，Wang B，Wang X，et al. NANOGP8 is the key regulator of stemness，EMT，Wnt pathway，chemoresistance，and other malignant phenotypes in gastric cancer cells [J]. PLoS One，2018，13（4）：e0192436.
[23] Zhang B，Yang Y，Shi X，et al. Proton pump inhibitor pantoprazole abrogates adriamycin-resistant gastric cancer cell invasiveness via suppression of Akt/GSK-β/β-catenin signaling and epithelial–mesenchymal transition [J]. Cancer Letters，2015，356（2）：704-712.
[24] Chen M，Huang SL，Zhang XQ，et al. Reversal effects of pantoprazole on multidrug resistance in human gastric adenocarcinoma cells by down-regulating the V-ATPases/mTOR/HIF-1alpha/P-gp and MRP1 signaling pathway in vitro and in vivo [J]. J Cell Biochem，2012，113（7）：2474-2487.
[25] Feng S，Zheng Z，Feng L，et al. Proton pump inhibitor pantoprazole inhibits the proliferation，selfrenewal and chemoresistance of gastric cancer stem cells via the EMT/betacatenin pathways [J]. Oncol Rep，2016，36（6）：3207-3214.
[26] Huang S，Chen M，Ding X，et al. Proton pump inhibitor selectively suppresses proliferation and restores the chemosensitivity of gastric cancer cells by inhibiting STAT3 signaling pathway [J]. Int Immunopharmacol，2013， 17（3）：585-592.
[27] Wen Z，Feng S，Wei L，et al. Evodiamine，a novel inhibitor of the Wnt pathway，inhibits the self-renewal of gastric cancer stem cells [J]. Int J Mol Med，2015，36（6）：1657-1663.
2019, Vol. 16 
京公网安备 11010502046598号