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CdTe quantum dots with daunorubicin induce apoptosis of multidrug-resistant human hepatoma HepG2/ADM cells: in vitro and in vivo evaluation.

Zhang G, Shi L, Selke M, Wang X - Nanoscale Res Lett (2011)

Bottom Line: Apoptotic staining, DNA fragmentation, and flow cytometry analysis further demonstrated that compared with Cdte QDs or DNR treatment alone, the apoptosis rate increased after the treatment of Cdte QDs together with DNR in HepG2/ADM cells.We observed that Cdte QDs treatment could reduce the effect of P-glycoprotein while the treatment of Cdte QDs together with DNR can clearly activate apoptosis-related caspases protein expression in HepG2/ADM cells.Thus, Cdte QDs combined with DNR may serve as a possible alternative for targeted therapeutic approaches for some cancer treatments.

View Article: PubMed Central - HTML - PubMed

Affiliation: State Key Lab of Bioelectronics (Chien-Shiung Wu Lab), Department of Biological Science and Medical Engineering Southeast University, Nanjing, 210096, PR China. xuewang@seu.edu.cn.

ABSTRACT
Cadmium telluride quantum dots (Cdte QDs) have received significant attention in biomedical research because of their potential in disease diagnosis and drug delivery. In this study, we have investigated the interaction mechanism and synergistic effect of 3-mercaptopropionic acid-capped Cdte QDs with the anti-cancer drug daunorubicin (DNR) on the induction of apoptosis using drug-resistant human hepatoma HepG2/ADM cells. Electrochemical assay revealed that Cdte QDs readily facilitated the uptake of the DNR into HepG2/ADM cells. Apoptotic staining, DNA fragmentation, and flow cytometry analysis further demonstrated that compared with Cdte QDs or DNR treatment alone, the apoptosis rate increased after the treatment of Cdte QDs together with DNR in HepG2/ADM cells. We observed that Cdte QDs treatment could reduce the effect of P-glycoprotein while the treatment of Cdte QDs together with DNR can clearly activate apoptosis-related caspases protein expression in HepG2/ADM cells. Moreover, our in vivo study indicated that the treatment of Cdte QDs together with DNR effectively inhibited the human hepatoma HepG2/ADM nude mice tumor growth. The increased cell apoptosis rate was closely correlated with the enhanced inhibition of tumor growth in the studied animals. Thus, Cdte QDs combined with DNR may serve as a possible alternative for targeted therapeutic approaches for some cancer treatments.

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Related in: MedlinePlus

Signal pathway analysis. (A) Western blotting analysis of P-gp in HepG2/ADM cells. HepG2/ADM cells without treatment were used as control (lane 1). Lysates were prepared from the cells treated 4 μM Cdte QDs with 4 × 10-6 mol/L DNR (lane 2). (B) The control cells without any treatment (1). The images were taken from cells treated with 4 μM Cdte QDs with 4 × 10-6 mol/L DNR for 72 h (2). Bar, 20 μm. (C) Western blotting analysis of cytochrome c released in HepG2/ADM cells: group 1, control group (lane 1); group 2, 4 × 10-6 mol/L DNR (lane 2); group 3, 4 μM Cdte QDs (lane 3); and group 4, 4 μM Cdte QDs with 4 × 10-6 mol/L DNR (lane 4). The following antibodies were used: anti-cleaved caspase-9, anti-cleaved caspase-3, and anti-PARP antibody. GAPDH was served as a loading control.
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Figure 6: Signal pathway analysis. (A) Western blotting analysis of P-gp in HepG2/ADM cells. HepG2/ADM cells without treatment were used as control (lane 1). Lysates were prepared from the cells treated 4 μM Cdte QDs with 4 × 10-6 mol/L DNR (lane 2). (B) The control cells without any treatment (1). The images were taken from cells treated with 4 μM Cdte QDs with 4 × 10-6 mol/L DNR for 72 h (2). Bar, 20 μm. (C) Western blotting analysis of cytochrome c released in HepG2/ADM cells: group 1, control group (lane 1); group 2, 4 × 10-6 mol/L DNR (lane 2); group 3, 4 μM Cdte QDs (lane 3); and group 4, 4 μM Cdte QDs with 4 × 10-6 mol/L DNR (lane 4). The following antibodies were used: anti-cleaved caspase-9, anti-cleaved caspase-3, and anti-PARP antibody. GAPDH was served as a loading control.

Mentions: Treatment of human HepG2/ADM cells with Cdte QDs + DNR for 72 h caused decrease in the amount of P-gp protein expression compared with control treatment (Figure 6A). Cdte QDs + DNR treated cell monolayers and immunostaining signals of P-gp protein were reduced and disrupted (Figure 6B). To further understand the molecular mechanisms underlying the synergistic effects of Cdte QDs + DNR-mediated apoptosis in HepG2r/ADM cells, we investigated apoptosis-related protein expression in the cells (Figure 6C). DNR or Cdte QDs cannot induce apoptosis strongly in HepG2r/ADM cells due to multidrug resistance. Interestingly, combined treatment of Cdte QDs + DNR strongly caused cytochrome c to be released into the cytosol and significantly activated caspase-9 and caspase-3 and induced degradation of its substrates, PARP. These data suggest that Cdte QDs with DNR treatment involve the release of cytochrome c from the mitochondria, which subsequently causes apoptosis by activation of caspase-9, 3 in HepG2r/ADM cells.


CdTe quantum dots with daunorubicin induce apoptosis of multidrug-resistant human hepatoma HepG2/ADM cells: in vitro and in vivo evaluation.

Zhang G, Shi L, Selke M, Wang X - Nanoscale Res Lett (2011)

Signal pathway analysis. (A) Western blotting analysis of P-gp in HepG2/ADM cells. HepG2/ADM cells without treatment were used as control (lane 1). Lysates were prepared from the cells treated 4 μM Cdte QDs with 4 × 10-6 mol/L DNR (lane 2). (B) The control cells without any treatment (1). The images were taken from cells treated with 4 μM Cdte QDs with 4 × 10-6 mol/L DNR for 72 h (2). Bar, 20 μm. (C) Western blotting analysis of cytochrome c released in HepG2/ADM cells: group 1, control group (lane 1); group 2, 4 × 10-6 mol/L DNR (lane 2); group 3, 4 μM Cdte QDs (lane 3); and group 4, 4 μM Cdte QDs with 4 × 10-6 mol/L DNR (lane 4). The following antibodies were used: anti-cleaved caspase-9, anti-cleaved caspase-3, and anti-PARP antibody. GAPDH was served as a loading control.
© Copyright Policy - open-access
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC3211514&req=5

Figure 6: Signal pathway analysis. (A) Western blotting analysis of P-gp in HepG2/ADM cells. HepG2/ADM cells without treatment were used as control (lane 1). Lysates were prepared from the cells treated 4 μM Cdte QDs with 4 × 10-6 mol/L DNR (lane 2). (B) The control cells without any treatment (1). The images were taken from cells treated with 4 μM Cdte QDs with 4 × 10-6 mol/L DNR for 72 h (2). Bar, 20 μm. (C) Western blotting analysis of cytochrome c released in HepG2/ADM cells: group 1, control group (lane 1); group 2, 4 × 10-6 mol/L DNR (lane 2); group 3, 4 μM Cdte QDs (lane 3); and group 4, 4 μM Cdte QDs with 4 × 10-6 mol/L DNR (lane 4). The following antibodies were used: anti-cleaved caspase-9, anti-cleaved caspase-3, and anti-PARP antibody. GAPDH was served as a loading control.
Mentions: Treatment of human HepG2/ADM cells with Cdte QDs + DNR for 72 h caused decrease in the amount of P-gp protein expression compared with control treatment (Figure 6A). Cdte QDs + DNR treated cell monolayers and immunostaining signals of P-gp protein were reduced and disrupted (Figure 6B). To further understand the molecular mechanisms underlying the synergistic effects of Cdte QDs + DNR-mediated apoptosis in HepG2r/ADM cells, we investigated apoptosis-related protein expression in the cells (Figure 6C). DNR or Cdte QDs cannot induce apoptosis strongly in HepG2r/ADM cells due to multidrug resistance. Interestingly, combined treatment of Cdte QDs + DNR strongly caused cytochrome c to be released into the cytosol and significantly activated caspase-9 and caspase-3 and induced degradation of its substrates, PARP. These data suggest that Cdte QDs with DNR treatment involve the release of cytochrome c from the mitochondria, which subsequently causes apoptosis by activation of caspase-9, 3 in HepG2r/ADM cells.

Bottom Line: Apoptotic staining, DNA fragmentation, and flow cytometry analysis further demonstrated that compared with Cdte QDs or DNR treatment alone, the apoptosis rate increased after the treatment of Cdte QDs together with DNR in HepG2/ADM cells.We observed that Cdte QDs treatment could reduce the effect of P-glycoprotein while the treatment of Cdte QDs together with DNR can clearly activate apoptosis-related caspases protein expression in HepG2/ADM cells.Thus, Cdte QDs combined with DNR may serve as a possible alternative for targeted therapeutic approaches for some cancer treatments.

View Article: PubMed Central - HTML - PubMed

Affiliation: State Key Lab of Bioelectronics (Chien-Shiung Wu Lab), Department of Biological Science and Medical Engineering Southeast University, Nanjing, 210096, PR China. xuewang@seu.edu.cn.

ABSTRACT
Cadmium telluride quantum dots (Cdte QDs) have received significant attention in biomedical research because of their potential in disease diagnosis and drug delivery. In this study, we have investigated the interaction mechanism and synergistic effect of 3-mercaptopropionic acid-capped Cdte QDs with the anti-cancer drug daunorubicin (DNR) on the induction of apoptosis using drug-resistant human hepatoma HepG2/ADM cells. Electrochemical assay revealed that Cdte QDs readily facilitated the uptake of the DNR into HepG2/ADM cells. Apoptotic staining, DNA fragmentation, and flow cytometry analysis further demonstrated that compared with Cdte QDs or DNR treatment alone, the apoptosis rate increased after the treatment of Cdte QDs together with DNR in HepG2/ADM cells. We observed that Cdte QDs treatment could reduce the effect of P-glycoprotein while the treatment of Cdte QDs together with DNR can clearly activate apoptosis-related caspases protein expression in HepG2/ADM cells. Moreover, our in vivo study indicated that the treatment of Cdte QDs together with DNR effectively inhibited the human hepatoma HepG2/ADM nude mice tumor growth. The increased cell apoptosis rate was closely correlated with the enhanced inhibition of tumor growth in the studied animals. Thus, Cdte QDs combined with DNR may serve as a possible alternative for targeted therapeutic approaches for some cancer treatments.

No MeSH data available.


Related in: MedlinePlus