Title

Multidrug resistance reversal activity of total alkaloid from Fritillaria thunbergii on cisplatin-resistant human lung adenocarcinoma A549/DDP cells

Department

Health Promotion

Document Type

Article

Publication Source

Chinese Journal of Pharmacology and Toxicology

Publication Date

2013-06-01

Volume

27

Issue

3

First Page

315

Last Page

320

Abstract

OBJECTIVE: To explore the effect of total alkaloid from Fritillaria thunbergii (TAF) on reversing multidrug resistance (MDR) of human lung adenocarcinoma A549/DDP cells. METHODS: Circled digit one In vitro Cytoxicity and proliferation inhibitory rate of TAF (12.5-200 mg·L-1) was assessed by MTT method. TAF 9 mg·L-1 was used in subsequent reversal experiments. Cyclosporine A (Cys A) 1 mg·L-1 and tetrandrine (Tet) 1 mg·L-1 acted as positive control group. The amount of MDR1 mRNA and P-glycoprotein (P-gp) of A549/DDP cells was measured by real time polymerase chain reaction and Western blotting, respectively. Circled digit two In vivo BALB/c nude mice were used to establish an A549/DDP tumor model. The mice were randomly divided into vehicle, DDP 5 mg·kg-1, TAF 2 mg·kg-1, DDP 5 mg·kg-1 plus TAF 0.5, 1 and 2 mg·kg-1 groups. DDP was ip given every two days and TAF was ig given once a day. Tumor volume was measured every four days and tumor mass was detected after 13 d. RESULTS: After incubation with TAF for 72 h, IC50 of TAF to A549 and A549/DDP cells was 141±5 and (298±22) mg·L-1, respectively, and IC10 of TAF to A549 and A549/DDP cells was 15.3±1.9 and (9.0±1.2) mg·L-1. IC50 of DDP without or with TAF 9 mg·L-1 on A549/DDP cells was 14.06±3.72 and (0.79±0.14)mg·L-1, respectively, while there was no significant change in IC50 of A549 cells. TAF reversed DDP resistance of A549/DDP cells with fold-reversal 17.80, which was higher than that of Cys A (10.16) and Tet (14.05). Compared with A549/DDP cell vehicle group, MDR1 mRNA and P-gp expression in A549/DDP cells was decreased by TAF (P<0.01). The tumor inhibitory rate of DDP 5 mg·kg-1 in vivo was 49.9%. The combination of DDP 5 mg·kg-1 and TAF2 mg·kg-1 increased the tumor inhibition rate to 67.4%. CONCLUSION: TAF enhances MDR reversal effect of DDP on A549/DDP cells in vitro and in vivo, and down-regulates MDR1 mRNA and P-gp expression in A549/DDP cells.

Keywords

Fritillaria thunbergii, Multidrug resistance, P-glycoprotein, Total alkaloid

DOI

10.3867/j.issn.1000-3002.2013.03.002

https://doi.org/10.3867/j.issn.1000-3002.2013.03.002

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