关键词:

结直肠癌, 化疗耐药, GTP 酶Rab25, 顺铂, 5?氟尿嘧啶

Abstract:

Objective To study the relationship between GTPase Rab25 and chemotherapy resistance in colorectal cancer. Methods MTT colorimetric method was used to detect the drug resistance of cells. Whole tran⁃ scriptome sequencing technology was used to screen the GTPase Rab family genes related to the drug resistance of colorectal cancer cells. Bioinformatics was used to analyze the correlation of Rab25 with patient prognosis and multi⁃ drug resistance biomarkers. RT⁃PCR and Western Blot were used to verify the RNA and protein expression level of Rab25 in cells. Flow cytometry was used to detect the cycle and apoptosis of drug⁃resistant cells before and after the overexpression of Rab25. Results The cell survival rate of drug⁃resistant strains was significantly higher than that of parental strains treated with anticancer drugs（P < 0.01）. Rab25，Rab32，and Rab38 were significantly lower expressed in drug⁃resistant strains（P < 0.001）. Colorectal cancer patients with high expression of Rab25 had a longer overall survival（HR = 0.4，P < 0.05）and Rab25 was negatively correlated with the expression of multidrug resis⁃ tance markers ABCB1，ABCC1 and ABCG2（P < 0.01）. Compared with HCT⁃8，the RNA and protein level of the drug⁃resistant strain Rab25 was significantly reduced，and the RNA and protein level of the drug⁃resistant strain was significantly increased after transfection of the Rab25 plasmid（P < 0.001）. Up ⁃ regulation of Rab25 enhanced the sensitivity of drug⁃resistant cells to drugs（P < 0.001）. Up⁃regulation of Rab25 enhanced drug⁃resistant cell G0/G1 blockade，and promoted drug⁃induced apoptosis of drug⁃resistant cells Effect（P < 0.001）. Conclusion Up⁃regulation of Rab25 can significantly reduce the chemotherapy resistance of colorectal cancer drug⁃resistant cell lines. 

Key words:

colorectal cancer, chemotherapy resistance, GTPase Rab25, cisplatin, 5?fluorouracil ,