外泌体在胃癌远处转移和耐药性中的研究进展

doi:10.3969/j.issn.1006-5725.2024.06.024

Abstract

Abstract:

Gastric cancer （GC） is one of the most common tumors and the fourth leading cause of cancer-related death worldwide.Due to the lack of specific signs in early GC， most cases are diagnosed at an advanced stage， often accompanied by infiltration and distant metastasis. Although chemotherapy is the most commonly used treatment for gastric cancer， due to the emergence of drug resistance， many patients will still relapse after chemotherapy， resulting in poor prognosis.Exosome （EXOs） in the Tumor micro environment （TME） can participate in intercellular communication and play an important role in GC distant metastasis and drug resistance. At present， the detailed mechanism of GC distant metastasis and drug resistance is still unclear. Identifying the exosome-induced mechanism involved in GC distant metastasis and drug resistance can help us find more reliable treatment methods for GC metastasis and drug resistance.This article reviews the mechanism of exosome in GC distant metastasis and drug resistance， in order to provide help for the diagnosis， treatment and research of GC.

Key words: gastric cancer, exosomes, metastasis, drug resistance, chemotherapy

CLC Number:

R735.2

Shu CHEN,Jinglei ZHANG,Kang RONG,Nan ZHANG,Weiyi SUN. Research progress of exosomes in distant metastasis and drug resistance of gastric cancer[J]. The Journal of Practical Medicine, 2024, 40(6): 870-876.

Figures/Tables 4

Fig.1

Fig.2

Tab.1

Exosomes involved in distant metastasis of gastric cancer"

外泌体来源	外泌体类型	受体细胞	作用靶点	转移器官	作用机制	促进/ 抑制	研究对象	肿瘤造模位置	参考
胃癌细胞	miR-106a	人腹膜间皮细胞HMrSV7	Smad7	腹膜	激活TGF-β/ Smad7通路、 MMT	促进	雄性BALB/c裸鼠、人胃癌细胞（AGS、BGC-823、MKN-45、 MKN-74、NCI-N87）、人腹膜间皮细胞HMrSV5	后腿皮下	［18］
胃癌细胞	miR-106a	人胃癌细胞NCI-N87	Smad7、 TIMP2	腹膜	激活TGF-β/ Smad7通路、 MMT	促进	雄性BALB/c裸鼠、人胃癌细胞（AGS、BGC-823和NCI-N87）、人腹膜间皮细胞HMrSV5	前腿右侧皮下	［19］
胃癌细胞	NNMT	人腹膜间皮细胞HMrSV5	-	腹膜	激活TGF-β/ Smad2通路	促进	人胃癌细胞株（GC-114、GC-026、MKN45和SNU-16）、人正常胃黏膜上皮细胞株GES-1、人腹膜间皮细胞HMrSV5	-	［20］
间充质干细胞（MSC）	miR-29b	MSC系UE6E7T-12	TGF-β1	腹膜	阻断TGF-β1 通路、MMT	抑制	C57BL/6N小鼠、NUGC-4人胃癌细胞、MSC系UE6E7T-12	-	［12］
胃癌细胞	miR-519a-3p	肝内巨噬细胞	DUSP2	肝脏	促进肝内巨噬细胞的M2样极化、促进血管生成、激活MAPK/ ERK通路	促进	雌性小鼠、人胃上皮细胞系GES -1 和GC细胞系（MKN45、MKN45-HL、HGC-27、NCI-N87）、KATOIII和AGS	前肢的腋窝、脾脏	［13］
胃癌细胞	circRNAUBE2Q2	-	miR-370-3p	肝脏	抑制自噬并促进糖酵解，激活 STAT3信号通路和EMT	促进	雌性BALB/c裸鼠、人GC细胞系BGC-823、SGC-7901、MKN-45、 MGC-803、HGC-27和正常GES-1 胃黏膜上皮细胞系	腹股沟区域皮下、肝门静脉	［21］
胃癌细胞	-	MGC803、MKN45细胞	-	肺脏	-	促进	BALB/c小鼠、MKN45、MKN31、MGC31、MGC803细胞	尾静脉	［23］
胃癌细胞	LINC01091	HGC-27、MKN45	miR-128-3p	肺脏	miR-128-3p/ ELF4/CDX2轴	促进	雄性BALB/c裸鼠、人胃癌细胞系（NCI-N87和AGS）、人胚肾细胞系HEK293T、HGC细胞株HGC-27、MKN45及人正常胃黏膜细胞株GES-1	皮下、尾静脉	［24］
胃癌细胞	miR-92a-3p	肺巨噬细胞	PD-L1	肺脏	激活ERK信号通路、诱导免疫抑制性巨噬细胞极化	促进	雌性C57BL/6N、小鼠前胃癌（MFC）细胞系、肺癌细胞系 LLC细胞、巨噬细胞	尾静脉	［22］
胃癌细胞	circFCHO2	HGC-3和AGS细胞	miR-194-5p	肺脏	激活JAK194/ STAT5通路	促进	BALB/c裸鼠、GC细胞系（MKN28， HGC-27，MKN45和AGS）	背部右侧皮下、尾静脉	［25］
胃癌细胞	hsa_circ_0000437	人淋巴内皮细胞HLECs	HSPA2	淋巴结	激活HSPA2-ERK 信号通路	促进	雌性裸鼠、HGC-27细胞、MKN-1 细胞和MKN-45细胞、GES-1细胞、 BGC-823细胞、人淋巴内皮细胞HLECs	足底皮下	［27］
高度淋巴转移的胃癌细胞	CD44	HGC-27、AGS	RhoA	淋巴结	调节RhoA/ YAP/Prox1/ CPT1A信号轴	促进	雄性BALB/c裸鼠、胃癌细胞系 AGS和HGC-27	足底皮下	［28］

Tab.1

Tab. 2

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外泌体来源	外泌体类型	受体细胞	作用靶点	耐药药物名称	耐药性	机制	研究对象	动物造模位置	参考
BGC823/DDP	miR-769-5p	BGC823、 BGC9	CASP9	DDP	促进	促p53 蛋白泛素化、抑制凋亡	BALB/c裸鼠、BGC823、BGC823/DDP细胞、 BGC9细胞	皮下	［32］
TAM	LncRNA CRNDE	MFC、 SGC7901	PTEN和 NEDD4-1	DDP	促进	促进PTEN泛素化、抑制凋亡	BALB/c雄性裸鼠、小鼠GC细胞系MFC和人GC细胞系SGC7901、MGC-803	皮下	［33］
CAF	miR-522	SGC7901、 MGC803、 MKN45	ALOX15	DDP、 PTX	促进	抑制铁死亡，参与泛素-蛋白酶体途径	BALB/c雄性裸鼠、人胃癌细胞系SGC7901、 MGC803细胞和MKN45细胞	皮下	［34］
HGC-27/DDP、AGS/DDP	circ-LDLRAD3	-	miR-588	DDP	促进	上调SOX5	BALB/c雌性裸鼠、GC细胞（NCI-N87，HGC-27和AGS），HGC-27/DDP、 AGS/DDP	皮下	［36］
HGC-27/OXA、AGS/OXA	Circ_0032821	HGC-27 和AGC	miR-515-5p	L-OHP	促进	上调SOX9	雄性BALB/C裸鼠、GC细胞系（HGC-27和AGS）、HGC-27/OXA和AGS/ OXA	右侧皮下	［37］
HGC27/PTX、KATOIII/PTX	-	HGC27和 KATOIII	-	PTX	促进	促进P-gp的过表达	AGS，HGC27，KATOⅢ和NCI-N87	-	［39］
SGC-7901、MGC-803	miR-107	SGC-7901/5-FU 和SGC-7901/DDP	HMGA2	5-FU、 DDP	抑制	抑制P-gp的表达水平	SGC-7901/5-FU和SGC-7901/DDP、MGC-803和HEK 293 T细胞系	-	［40］
CAF	IL-8	HGC-27和AGS	-	L-OHP	促进	激活PI3K/AKT途径	BALB/c裸鼠、人胃癌细胞株HGC-27和AGS、 CAF	皮下	［42］
HGC-27/OXA	circ_0091741	HGC-27	miR-330-3p	L-OHP	促进	Wnt/β-连环蛋白轴	人正常胃黏膜上皮细胞株GES-1和胃癌细胞株（AGS、HGC-27、MKN-45、MKN-74和NCI-N87）、HGC-27/OXA细胞	右背部皮下	［11］

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Research progress of exosomes in distant metastasis and drug resistance of gastric cancer

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