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Retinoblastoma tumor suppressor gene 1 enhances 5-Fluorouracil chemosensitivity through SDF-1/CXCR4 axis by regulating autophagy in gastric cancer
- Source :
- Pathology - Research and Practice. 224:153532
- Publication Year :
- 2021
- Publisher :
- Elsevier BV, 2021.
-
Abstract
- Due to lack of effective biomarkers for early diagnosis, most patients are diagnosed with advanced gastric cancer and have lower survival rates. 5-Fluorouracil (5-FU) is one of commonly used drugs for chemotherapy of gastric cancer, but drug resistance limits the wide application of agents. Retinoblastoma tumor suppressor gene 1 (RB1) is a key regulator in the progression of various human cancers, including gastric cancer. However, the effects of RB1 on chemosensitivity and the underlying mechanisms in gastric cancer (GC) are not clear. In this study, expressions of RB1 in GC cell lines were evaluated by RT-qPCR and western blot assay. CCK-8 was applied to examine the effect of 5-FU on cell viability. Meanwhile, IC50 values were calculated. The drug-resistance protein MDR1 and autophagy-related proteins were detected by western blot assay. Flow cytometry was used to detect cell cycle. The results showed that RB1 expressions were downregulated in GC cell lines and had significant differences between 5-FU resistance cell lines (SNU-620/5-FU and NUGC-3/5-FU) and non-resistance cell lines (SNU-620 and NUGC-3). Overexpression of RB1 enhanced 5-FU sensitivity of GC cells and caused cell cycle arrest in the S phase. Meanwhile, autophagy-related proteins were downregulated. Mechanistically, SDF-1/CXCR4 participated in the regulation of RB1 on cell autophagy. Autophagy activator, SDF-1 treatment and CXCR4 activation reversed the promoted effects of RB1 on 5-FU sensitivity in GC cells. In conclusion, our data revealed that RB1 was downregulated in GC cell lines. RB1 overexpression enhanced 5-FU chemosensitivity in GC cells by regulating cell autophagy via SDF-1/CXCR4 pathway. RB1 might serve as a promising therapeutic target of GC.
- Subjects :
- 0301 basic medicine
Receptors, CXCR4
Cell cycle checkpoint
Tumor suppressor gene
Retinal Neoplasms
Cell
Apoptosis
Pathology and Forensic Medicine
03 medical and health sciences
0302 clinical medicine
Stomach Neoplasms
Cell Line, Tumor
Autophagy
medicine
Humans
Viability assay
Retinoblastoma
Chemistry
Cancer
Cell Biology
Cell cycle
medicine.disease
Chemokine CXCL12
eye diseases
030104 developmental biology
medicine.anatomical_structure
Drug Resistance, Neoplasm
030220 oncology & carcinogenesis
Cancer research
Fluorouracil
Signal Transduction
Subjects
Details
- ISSN :
- 03440338
- Volume :
- 224
- Database :
- OpenAIRE
- Journal :
- Pathology - Research and Practice
- Accession number :
- edsair.doi.dedup.....183cdf60f2075cb92b537384938b2d60