O PAPEL DO GENE MDR-1 E A GLICOPROTEÍNA-P NA INTOXICAÇÃO POR IVERMECTINA EM CÃES - REVISÃO

A classe das avermectinas são muito utilizadas na medicina veterinária como antiparasitários, sendo a ivermectina um dos medicamentos representantes. A ivermectina possui alta solubilidade, o que contribui para que seja distribuída pelo organismo dos animais com maior facilidade. O gene MDR1 (ABCB1), é conhecido como o gene relacionado à multirresistência às drogas, sendo responsável pela expressão da glicoproteína-P (P-gP), que é encontrada em diversos tipos celulares, sendo importante nas barreiras naturais. Quando há alterações no gene há falha na expressão da P-gP, o que permite com que haja o aumento da absorção de fármacos, levando à intoxicação em animais. O objetivou-se do presente trabalho analisar a prevalência dos alelos para a mutação do gene em diferentes raças e localizações. Como a ivermectina permanece no organismo por um grande período, principalmente no fígado, músculo e gordura, torna-se um problema para os portadores dos alelos. Portanto, é essencial a responsabilidade quanto a prescrição desse medicamento à cães, uma vez que o número de intoxicações causadas pelo uso desse antiparasitário é representativo. Também é importante a intervenção para a reprodução racional da espécie.

A Ferrocene Derivative Reduces Cisplatin Resistance in Breast Cancer Cells through Suppression of MDR-1 Expression and Modulation of JAK2/STAT3 Signaling Pathway

Background: Breast cancer is the most common kind of cancer among women in the world. Despite major cancer therapy successes in recent years, cancer cells usually develop mechanisms to survive chemotherapy- induced cell death. Therefore, new strategies are needed to reverse cancer chemoresistance. Objective: The aim of this study was to investigate the effect of a recently-synthesized ferrocene derivative named 1-ferrocenyl-3-(4-methylsulfonylphenyl)propen-1-one (FMSP) on cisplatin resistance in MCF-7 cells, focusing on its inhibitory effects on Multi-Drug Resistance-1 (MDR-1) and inflammatory-related STAT3 pathway. Methods: Cisplatin-resistant MCF-7 cells were developed and the effect of cisplatin and FMSP on cell viability was examined by MTT assay. RT-PCR and Western blotting analyses were performed to assess the gene and protein expression of MDR-1 as well as phosphorylation of JAK2 and STAT3. Results: Overexpression of MDR1 as well as a marked increase in the level of phosphorylated STAT3 was observed in cisplatin-resistant MCF-7 (MCF-7R) cells. FMSP successfully reduced the MCF-7R cell viability and reversed both MDR1 expression and STAT3 phosphorylation status through which sensitivity of MCF-7R cells to cisplatin treatment was regained. Conclusion: Our results indicated that FMSP may be considered as a promising therapeutic agent for the prevention and management of chemoresistance in breast cancer cells.

Anticarcinogenic Effects of Capsaicin-Loaded Nanoparticles on In Vitro Hepatocellular Carcinoma

Background:: Hepatocellular carcinoma (HCC) is the fifth most frequent cancer worldwide with a low overall survival due to high metastasis and recurrence rates. The aim of this study is to assess and compare the possible anti-neoplastic effect of capsaicin and nanoformulated capsaicin on in vitro HCC human cell line HepG2. Materials and Methods:: Capsaicin-loaded trimethyl chitosan nanoparticles (CL TMCS NPs) were synthesized by iontropic gelation of cationic TMCS with capsaicin. The synthesized nanoparticles were characterized through TEM, and zeta analyzer. Human hepatocarcinoma HepG2 cell lines were cultured and treated with 50, 75 & 100 μM of capsaicin (CAP), plain TMCS NPs and CL-NPs as well as ethanol (control) for 24h and 48h. The induced effects were investigated by flow cytometry, immunocytochemistry assay for Bcl-2, Bax, and caspase proteins and evaluating gene expression levels of Bcl-2, Bax, and MDR-1 mRNA by real-time PCR. Results:: Our results demonstrated that capsaicin- loaded NPs had the potential to significantly increase capsaicin bioactivity compared with the plain capsaicin formulation either in inducing apoptosis through altering expression of apoptotic regulators or modifying MDR-1 expression. Conclusions:: TMCs nanoparticles investigated in this study may be a good drug delivery vehicle for capsaicin. Application of capsaicin-loaded NPs in HCC management as an adjunct therapeutic approach may be a novel strategy to improve the treatment efficacy and resistance of the conventionally used chemotherapy.

T4 Reduces Cisplatin Resistance by Inhibiting AEG-1 Gene Expression in Lung Cancer Cells

BackgroundLung cancer is one of the deadliest diseases in the world. Most lung cancer patients are resistant to chemotherapy drugs. In our study, we investigated whether T4 can reduce the resistance of lung cancer cells to chemotherapeutic drugs through the action of AEG-1.Materials and Methods1.A549 and A549/DDP cells were respectively transfected with overexpressing AEG-1 and knockdown AEG-1 plasmid. A549 and A549/DDP cells were added 0、25、50、100、200nM T4 respectively. 200nM T4 was selected for following experiments. A549/DDP cells were divided into A549/DDP empty group, T4 group, T4+AEG-1 overexpressing group. CCK8 assay was used to detect the proliferation of cells in each group. RT-qPCR and Western blotting were used to detect the expression of AEG-1 and MDR-1.ResultsAs expected, the expression of AEG-1 in A549 and A549/DDP cells is positively correlated with cisplatin resistance. When AEG-1 protein was overexpressed in A549 cells, the lethal effect of cisplatin on A549 cells was attenuated (all P<0.05). After AEG-1 protein was knocked down in A549/DDP cells, cisplatin was applied to the A549/DDP cells. The lethal effect was significantly increased compared to that in the control cells (all P<0.05). The expression of AEG-1 protein gradually decreased with increasing concentration of T4 in A549 and A549/DDP cells; The resistance to cisplatin was reduced after the addition of T4 to A549/DDP cells (P<0.05), and this effect was enhanced after transfection with the AEG-1 plasmid. ConclusionIn summary, T4 is important for increasing the sensitively of lung cancer cells to cisplatin. AEG-1 may be a key protein involved in this effect and may have an important impact on the survival rate of chemotherapy in patients with lung cancer in the future.