Mechanism Research of Reversal of Multidrug Resistance by the Application of 5-Bromotetrandrine and Magnetic Nanoparticle of Fe3O4 Combined with Daunorubicin in a Human-Nude Mice Xenograft Model

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 5058-5058
Author(s):  
Bao-An Chen ◽  
Ya-nan Wu ◽  
Jian Cheng ◽  
Feng Gao ◽  
Wen-lin Xu ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Nude Mice ◽  
Magnetic Nanoparticle ◽  
Multiple Drug Resistance ◽  
Xenograft Model ◽  
Tumor Formation ◽  
Multiple Drug ◽  
Inhibition Rate ◽  
Group 5

Abstract Objective: To establish the xenograft leukemia model with stable multiple drug resistance in nude mice; to investigate the reversal effect of 5-Bromotetrandrine and Magnetic nanoparticle of Fe3O4 combined with DNR in vivo and to search for the possible reversal mechanisms. Methods: K562 and K562/A02 cells were respectively inoculated subcutaneously into back of athymic nude mice (1×107 cells/each) to establish the xenograft models. The tumor formation was evaluated by animal ultrasonic inspection. Tumors-bearing nude mice were assigned randomly to five groups which were treated with NS (A group); DNR 1mg/kg (B group); nanoparticle of Fe3O4 combined with DNR 0.63mg/kg(C group): 5-BrTet 2.5mg/kg combined with DNR(D group); 5-Bromotetrandrine 2.5mg/kg and Magnetic nanoparticle of Fe3O4 combined with DNR 0.63mg/kg(E group) respectively. The incidence of tumor formation, growth characteristics, weight and volume of tumor were observed. The histopathologic examination of tumors and organs were detected. For resistant tumors, the protein levels of P-glycoprotein (P-gp) were detected by Western blot. Results: The tumor incidence was 100% in the nude mice inoculated with either K562 or K562/A02 cells. In 6 to 9 days,the tumors reached a volume of more than 1 00 mm3. In vivo, MTT assay showed K562/A02 tumor maintained the drug resistance. For K562 cells xenograft tumors, there were no apparent differences in tumor suppression effect between the B AC AD AE group. For K562/A02 cells xenograft tumors, 5-BrTet and Magnetic nanoparticle of Fe3O4 combined with DNR significantly suppressed growth of tumor: the inhibition rate was 62.76% while DNR alone be used, the inhibition rate was 3.68%. Pathologic examination of resistant tumors showed the tumors necrosis obviously in E group. Application of 5-BrTet and Magnetic nanoparticle of Fe3O4 inhibited the overexpression of P-gp. Conclusion: The xenograft leukemia nude mice model was maintain the multiple drug resistance. 5-Bromotetrandrine and Magnetic nanoparticle of Fe3O4 combined with DNR had a significant tumor-suppressing effect on MDR leukemia cells xenograft model.

Replicative fitness in vivo of HIV-1 variants with multiple drug resistance-associated mutations

2001 ◽  
Vol 65 (2) ◽  
pp. 218-224 ◽  
Author(s):  
Helen L. Devereux ◽  
Vincent C. Emery ◽  
Margaret A. Johnson ◽  
Clive Loveday
Keyword(s):  
Drug Resistance ◽  
Multiple Drug Resistance ◽  
Multiple Drug ◽  
Replicative Fitness ◽  
Hiv 1

scholarly journals MDA-9/Syntenin (SDCBP) Is a Critical Regulator of Chemoresistance, Survival and Stemness in Prostate Cancer Stem Cells

Cancers ◽  
2019 ◽  
Vol 12 (1) ◽  
pp. 53 ◽  
Author(s):  
Sarmistha Talukdar ◽  
Swadesh K. Das ◽  
Anjan K. Pradhan ◽  
Luni Emdad ◽  
Jolene J. Windle ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Stem Cells ◽  
Drug Resistance ◽  
Stem Cell ◽  
Cancer Stem Cells ◽  
Multiple Drug Resistance ◽  
Trichostatin A ◽  
Tumor Formation ◽  
Multiple Drug ◽  
Prostate Cancer Stem Cells

Despite some progress, treating advanced prostate cancer remains a major clinical challenge. Recent studies have shown that prostate cancer can originate from undifferentiated, rare, stem cell-like populations within the heterogeneous tumor mass, which play seminal roles in tumor formation, maintenance of tumor homeostasis and initiation of metastases. These cells possess enhanced propensity toward chemoresistance and may serve as a prognostic factor for prostate cancer recurrence. Despite extensive studies, selective targeted therapies against these stem cell-like populations are limited and more detailed experiments are required to develop novel targeted therapeutics. We now show that MDA-9/Syntenin/SDCBP (MDA-9) is a critical regulator of survival, stemness and chemoresistance in prostate cancer stem cells (PCSCs). MDA-9 regulates the expression of multiple stem-regulatory genes and loss of MDA-9 causes a complete collapse of the stem-regulatory network in PCSCs. Loss of MDA-9 also sensitizes PCSCs to multiple chemotherapeutics with different modes of action, such as docetaxel and trichostatin-A, suggesting that MDA-9 may regulate multiple drug resistance. Mechanistically, MDA-9-mediated multiple drug resistance, stemness and survival are regulated in PCSCs through activation of STAT3. Activated STAT3 regulates chemoresistance in PCSCs through protective autophagy as well as regulation of MDR1 on the surface of the PCSCs. We now demonstrate that MDA-9 is a critical regulator of PCSC survival and stemness via exploiting the inter-connected STAT3 and c-myc pathways.

scholarly journals In vivo activity of anprocide alone, and in vitro activity in combination with conventional antibiotics against Staphylococcus aureus and Staphylococcus epidermidis biofilms

2009 ◽  
Vol 58 (9) ◽  
pp. 1203-1206 ◽  
Author(s):  
Robin K. Pettit ◽  
Christine A. Weber ◽  
Stacey B. Lawrence ◽  
George R. Pettit ◽  
Melissa J. Kean ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Drug Resistance ◽  
Murine Model ◽  
Staphylococcus Epidermidis ◽  
Multiple Drug Resistance ◽  
Multiple Drug ◽  
In Vitro Activity ◽  
Conventional Antibiotics

The alarming spread of multiple drug resistance in Staphylococcus aureus, combined with the frequent occurrence of S. aureus and Staphylococcus epidermidis in biofilm-type infections, indicates a growing need for new therapies. The experimental steroidal amide anprocide [3β-acetoxy-17β-(l-prolyl)amino-5α-androstane] significantly reduced c.f.u. ml−1 per suture (P <0.0001) in a murine model of topical S. aureus infection. In chequerboard assays with planktonic-grown S. aureus and S. epidermidis, anprocide was synergistic with bacitracin, oxacillin, clindamycin or ceftriaxone. Anprocide was also synergistic in combination with bacitracin or oxacillin against some isolates of biofilm-grown S. aureus and S. epidermidis.

miRNA 5100 Exacerbated Cisplatin Chemoresistance in Lung Cancer via Suppressing C/EBP Homologous Protein (CHOP) Expression

2021 ◽  
Vol 11 (1) ◽  
pp. 59-66
Author(s):  
Fang Zhang ◽  
Jili Zou ◽  
Dandan Huang
Keyword(s):  
Lung Cancer ◽  
Drug Resistance ◽  
A549 Cells ◽  
Xenograft Model ◽  
Tumor Grade ◽  
Tumor Formation ◽  
Cancer Drug ◽  
Therapeutic Effects ◽  
Chop Expression

This study intends to assess CHOP abundance in lung cancer tissues and drug-resistant cell lines, and the mechanisms of miRNA 5100 on lung cancer drug-resistance chemoresistance. Tumor tissues were collected to detect CHOP levels by immunohistochemical staining and PCR. IC50 of cisplatin and other drugs was detected by MTT assay in A549 or A549/CDDP cells. miR-5100 was overexpressed or knocked down by miR-5100 mimics or inhibitor followed by analysis of CHOP and related proteins abundances by Western blot. A549 cells were injected into mice to establish a xenograft model which was treated with cisplatin followed by detecting tumor growth. CHOP abundance presented substantial level in non-cancerous lung tissues, while miR-5100 level was significantly reduced with negative correlation with CHOP in cancer samples. Low CHOP expression was associated with increased tumor grade and death. IC50 of all tested drugs particularly cisplatin was increased in A549/CDDP or H446/CDDP cells, accompanied by reduced CHOP, LC3-II, DR5 and TRB3 mRNA and protein levels. miR-5100 mimics or miR-5100 inhibitor reduced or elevated CHOP level, accompanied by significantly reduced or elevated LC3-II, DR5, TRB3 level and sensitivity to cisplatin respectively. In addition, miR-5100 overexpression did not affect tumor formation but blemished therapeutic effects of cisplatin and reduced CHOP abundance in vivo. miR-5100 could suppress CHOP expression and regulate drug resistance related genes, ultimately exacerbating chemotherapeutic resistance in lung cancer cells.

scholarly journals Crizotinib and Doxorubicin Cooperatively Reduces Drug Resistance by Mitigating MDR1 to Increase Hepatocellular Carcinoma Cells Death

2021 ◽  
Vol 11 ◽  
Author(s):  
Ming Shao ◽  
Run Shi ◽  
Zhen-Xing Gao ◽  
Shan-Shan Gao ◽  
Jing-Feng Li ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Drug Resistance ◽  
Cell Death ◽  
Kinase Inhibitor ◽  
Multiple Drug Resistance ◽  
Autophagic Cell Death ◽  
Multiple Drug ◽  
Parp 1

As the sixth most lethal cancers worldwide, hepatocellular carcinoma (HCC) has been treated with doxorubicin (Dox) for decades. However, chemotherapy resistance, especially for Dox is an even more prominent problem due to its high cardiotoxicity. To find a regimen to reduce Dox resistance, and identify the mechanisms behind it, we tried to identify combination of drugs that can overcome drug resistance by screening tyrosine kinase inhibitor(s) with Dox with various HCC cell lines in vitro and in vivo. We report here that combination of Crizo and Dox has a synergistic effect on inducing HCC cell death. Accordingly, Crizo plus Dox increases Dox accumulation in nucleus 3-16 times compared to Dox only; HCC cell death enhanced at least 50% in vitro and tumor weights reduced ranging from 35 to 65%. Combining these two drugs reduces multiple drug resistance 1 (MDR1) protein as a result of activation of protein kinase RNA-like endoplasmic reticulum kinase (PERK), which phosphorylates eIF2α, leading to protein translational repression. Additionally, PERK stimulation activates C-Jun terminal kinase (JNK), resulting in accumulation of unfused autophagosome to enhance autophagic cell death via Poly-ADP-ribosyltransferase (PARP-1) cleavage. When the activity of PERK or JNK is blocked, unfused autophagosome is diminished, cleaved PARP-1 is reduced, and cell death is abated. Therefore, Crizo plus Dox sensitize HCC drug resistance by engaging PERK-p- eIF2α-MDR1, and kill HCC cells by engaging PERK-JNK- autophagic cell death pathways. These newly discovered mechanisms of Crizo plus Dox not only provide a potential treatment for HCC but also point to an approach to overcome MDR1 related drug resistance in other cancers.

Do Multiple Drug Resistance Transporters Interfere with Cell Functioning under Normal Conditions?

2020 ◽  
Vol 85 (12-13) ◽  
pp. 1560-1569
Author(s):  
D. A. Knorre ◽  
K. V. Galkina ◽  
T. Shirokovskikh ◽  
A. Banerjee ◽  
R. Prasad
Keyword(s):  
Drug Resistance ◽  
Multiple Drug Resistance ◽  
Multiple Drug
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