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Molecules 2016, 21(7), 852; doi:10.3390/molecules21070852

The Effects and Mechanisms of Periplaneta americana Extract Reversal of Multi-Drug Resistance in BEL-7402/5-FU Cells

1,†
,
1,†
,
1
,
1
,
2
and
1,3,*
1
College of Pharmacy and Chemistry, Dali University, Dali 671000, Yunnan, China
2
College of Pharmacy, Shanghai Jiaotong University, Shanghai 200240, China
3
Yunnan Provincial Key Laboratory of Entomological Biopharmaceutical R & D, Dali University, Dali 671000, Yunnan, China
These authors contributed equally to this study.
*
Author to whom correspondence should be addressed.
Academic Editor: Helena Vasconcelos
Received: 4 May 2016 / Revised: 22 June 2016 / Accepted: 24 June 2016 / Published: 28 June 2016
(This article belongs to the Special Issue New Approaches to Counteract Drug Resistance in Cancer)
View Full-Text   |   Download PDF [5530 KB, uploaded 28 June 2016]   |  

Abstract

The present study reports the reversing effects of extracts from P. americana on multidrug resistance of BEL-7402/5-FU cells, as well as a preliminary investigation on their mechanism of action. A methylthiazolyl tetrazolium (MTT) method was applied to determine the multidrug resistance of BEL-7402/5-FU, while an intracellular drug accumulation assay was used to evaluate the effects of a column chromatography extract (PACC) and defatted extract (PADF) from P. americana on reversing multi-drug resistance. BEL-7402/5-FU reflected high resistance to 5-FU; PACC and PADF could promote drug accumulation in BEL-7402/5-FU cells, among which PADF was more effective than PACC. Moreover, results from the immunocytochemical method showed that PACC and PADF could downregulate the expression of drug resistance-associated proteins (P-gp, MRP, LRP); PACC and PADF had no effects on the expression of multidrug resistance-associated enzymes (GST-π), but PACC could increase the expression of multidrug resistance-associated enzymes (PKC). Results of real-time fluorescence quantitative PCR revealed that PACC and PADF were able to markedly inhibit the expression of multidrug resistance-associated genes (MDR1, LRP and MRP1); PACC presented a significant impact on the gene expression of multidrug resistance-associated enzymes, which increased the gene expression of GST-π and PKC. However, PADF had little impact on the expression of multidrug resistance-associated enzymes. These results demonstrated that PACC and PADF extracted from P. americana could effectively reverse MDR in BEL-7402/5-FU cells, whose mechanism was to inhibit the expression of P-gp, MRP, and LRP, and that PADF was more effective in the reversal of MDR than did PACC. In addition, some of extracts from P. americana altered (sometimes increasing) the expression of multidrug resistance-associated enzymes. View Full-Text
Keywords: P. americana; reversion; hepatocellular carcinoma; multidrug resistance P. americana; reversion; hepatocellular carcinoma; multidrug resistance
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Yuan, F.; Liu, J.; Qiao, T.; Li, T.; Shen, Q.; Peng, F. The Effects and Mechanisms of Periplaneta americana Extract Reversal of Multi-Drug Resistance in BEL-7402/5-FU Cells. Molecules 2016, 21, 852.

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