Chlorophyllin increases the sensitivity of pancreatic cancer cells to gemcitabine treatment
10.3781/j.issn.1000-7431.2024.2407-0436
- VernacularTitle:叶绿素铜钠盐增加胰腺癌细胞对吉西他滨治疗的敏感性
- Author:
Jiaqiang REN
1
;
Shuai WU
;
Jiantao MO
;
Tong SU
;
Liang HAN
;
Zheng WANG
;
Zheng WU
Author Information
1. 西安交通大学第一附属医院肝胆外科,陕西 西安 710061
- Publication Type:Journal Article
- Keywords:
Pancreatic cancer;
Gemcitabine;
Chlorophyllin;
Sensitivity;
Resistance
- From:
Tumor
2024;44(11):1092-1103
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To investigate the effect of copper chlorophyllin sodium salt(CHL)on the sensitivity of human pancreatic cancer cells in response to gemcitabine(GEM)therapy and on the therapeutic effect on pancreatic cancer cells that have developed GEM resistance.Methods:MIA GR(a pancreatic cancer cell line resistant to GEM)was induced by a low-dose continuous incremental method,and the half inhibitory concentration(IC50)of MIA WT and MIA GR to GEM treatment was detected by the CCK-8 method,and the resistance index was calculated;the difference in IC50 of CHL on the two types of cells was detected by the CCK-8 method after treating MIA WT and MIA GR cells with different concentrations of CHL,CCK-8 method was used to detect the difference in IC50 of CHL on the two types of cells;on the basis of IC50,MIA WT and MIA GR cells were intervened with CHL and(or)GEM with different multiplicity of IC50,respectively,and the growth inhibition curves of MIA WT and MIA GR cells were detected by the CCK-8 method under the intervention of CHL combined with GEM;After the intervention of MIA WT and MIA GR cells with CHL and(or)GEM at IC50,respectively,the effects on the proliferation of the two different cells were detected using the clone formation assay;the effects on cytotoxicity/activity were observed under fluorescence microscopy;and the effects on apoptosis were detected using flow cytometry.Finally,western blotting was used to detect the effects of CHL and(or)GEM interventions on the drug resistance-associated molecules P-glycoprotein(P-gp)and ribonucleotide reductase regulatory subunit M2(RRM2)in MIA GR cells,the and sensitivity-related molecule deoxycytidine kinase(DCK)on protein expression levels.Results:MIA GR cells were verified to be well drug resistant,with resistance indices of 549.1 and 667.9 after 48 h and 96 h after GEM intervention compared to homologous wild-type MIA WT cells,respectively;CHL intervention inhibited the proliferation of MIA GR cells more significantly compared to that of MIA WT cells;and CHL in combination with GEM exerted a more significant growth inhibitory effect compared to GEM alone in both MIA WT cells(P<0.001)and MIA GR cells(P<0.01).CHL significantly inhibited the tumor proliferation of MIA GR cells,and the inhibitory effect was more pronounced in both cells when combined with GEM(P<0.000 1);furthermore,compared to GEM alone,the intervention with CHL could cause more pronounced cytotoxicity(P<0.000 1)in both MIA WT and MIA GR cells.caused more pronounced cytotoxicity(P<0.000 1)and induced a higher percentage of apoptosis than GEM alone.The results of the western blotting assay showed that CHL intervention caused a decrease in the expression levels of P-gp and RRM2 proteins,as well as an increase in the protein expression level of DCK in MIA GR cells.Conclusion:CHL increases the sensitivity of pancreatic cancer cells to GEM and also induces a decrease in the resistance of drug-resistant pancreatic cancer cells to GEM.
