Emodin reverses gemcitabine resistance of pancreatic cancer cell lines. - GreenMedInfo Summary
Emodin Reverses Gemcitabine Resistance of Pancreatic Cancer Cell Lines Through Inhibition of IKKβ/NF-κB Signaling Pathway.
Onco Targets Ther. 2020 ;13:9839-9848. Epub 2020 Oct 2. PMID: 33061461
Background: Pancreatic cancer is one of the most malignant tumors, and gemcitabine has been considered as the standard treatment and been widely utilized as a first-line drug for advanced pancreatic cancer, but gemcitabine-resistance always occurs after a short period of treatment.
Methods: Two pancreatic cancer cell lines Panc-1 and MIA-PaCa-2 were used as the study subject and their gemcitabine-resistant cells were established. Both drug-resistant cells were divided into four groups: blank, emodin, gemcitabine, and emodin+gemcitabine. Cell viability was detected by MTT assay. Flow cytometry was performed to detect cell apoptosis rate and P-gp function. Quantitative real-time polymerase chain reaction and Western blotting were used to detectmRNA/protein expressions, respectively. Electrophoretic mobility shift assay (EMSA) was performed to detectbinding activity. Rhodamine 123 efflux assay was used to detectfunction.
Results: Emodin could inhibit cell activity in all cell lines. Both emodin and gemcitabine can significantly increase the apoptosis rate, and the combination of the two drugs can further significantly increase the apoptosis rate in normal pancreatic cancer cell lines. In both drug-resistant pancreatic cancer cell lines, it can be observed that although gemcitabine can increase the apoptosis rate, the effect of promoting apoptosis is significantly lower than that of emodin; the drug combination can still significantly increase the apoptosis rate on the basis of emodin alone. Emodin can significantly reduce the mRNA and protein expression levels of, and, and significantly increase the mRNA and protein expression levels of. Emodin significantly reducedactivity and emodin significantly promotedfluorescence intensity from Rhodamine 123 efflux assay.
Conclusion: Emodin inhibits the expression of, thereby inhibiting the expression and activity of downstream, and inhibitsfunction at the same time, ultimately achieving the purpose of reversing the drug-resistance of pancreatic cancer cell lines.